MEDICAL FORMS AND BIOPHARMACY - VFUsis.vfu.cz/links/dvorackovakaterina-medical-forms-and-biopharmacy... · 1.5 Aromatic waters ... The aim of these practical classes from subject

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UNIVERSITY OF VETERINARY AND PHARMACEUTICAL SCIENCES BRNO

FACULTY OF PHARMACY Department of Pharmaceutics

MEDICAL FORMS

AND BIOPHARMACY I. Liquid and Semi-Solid Dosage Forms

Kateřina Dvořáčková

Aleš Franc

Jan Gajdziok

Martina Kejdušová

David Vetchý

BRNO 2014

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UNIVERSITY OF VETERINARY A PHARMACEUTICAL SCIENCES BRNO

FACULTY OF PHARMACY Department of Pharmaceutics

MEDICAL FORMS AND BIOPHARMACY

I. Liquid and Semi-Solid Dosage Forms

Doc. PharmDr. Kateřina Dvořáčková, Ph.D.

PharmDr. Aleš Franc, Ph.D.

PharmDr. Jan Gajdziok, Ph.D.

PharmDr. Martina Kejdušová, Ph.D.

Doc. PharmDr. Mgr. David Vetchý Ph.D.

BRNO 2014

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Content

1. Liquid preparations ............................................................................................................ 6

1.1 Liquid preparations for oral use ................................................................................... 6

1.2 Liquid preparations for cutaneous application .......................................................... 12

1.3 Pharmaceutical solutions ........................................................................................... 14

1.4 Syrups ........................................................................................................................ 29

1.5 Aromatic waters ......................................................................................................... 32

1.6 Mucilages ................................................................................................................... 36

1.7 Herbal drug preparations ........................................................................................... 39

1.8 Eye drops ................................................................................................................... 46

1.9 Eye lotions ................................................................................................................. 57

1.10 Nasal drops ............................................................................................................. 58

1.11 Ear drops ................................................................................................................ 62

1.12 Emulsions ............................................................................................................... 66

1.13 Suspensions ............................................................................................................ 76

2. Semi-solid preparations .................................................................................................... 86

2.1 Ointments ................................................................................................................... 94

2.2 Creams ..................................................................................................................... 110

2.3 Gels .......................................................................................................................... 119

2.4 Pastes ....................................................................................................................... 123

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PREFACE

The subject “Medical Forms and Biopharmacy” is offered in the curriculum of the

Pharmaceutical Faculty of the University of Veterinary and Pharmaceutical Sciences Brno

and taught by the Department of Pharmaceutics. Pharmaceutical technology is one of the

profile pharmaceutical disciplines, and it deals with the composition, formulation, production,

evaluation and quality assurance of drugs. It studies the conditions in which active substances

and pharmaceutical excipients are transformed into the final form of the medicinal product. It

also describes the various rules by which these processes are controlled, ensuring the

production of drugs maintains a level of declared efficiency, stability and safety. The

optimization of the technological process of drug production is as important a step as the

synthesis of active ingredients or the isolation of unknown compounds.

The main reason for the transformation of active substances into the form of medicinal

preparations is the requirement for a drug to be applied in safe and comfortable way, usually

by location and in a time-controlled manner.

The formulation and production of the final drug is often dependent upon pharmaceutical

excipients and their suitable selection. Constitutive excipients usually form the outer

appearance of the dosage form as well as its inner structure, and they control the application

of the drug, ensure the drug’s physico-chemical and microbiological stability, identify the

specific product and often regulate the sensory perception of the final product.

The identification of factors influencing the bioavailability of the active substance led to the

conclusion that medicine and its formulation play a key role in this issue. Pharmaceutical

technology, mainly due to the study of the relationship between the form of the medicinal

product and drug bioavailability, created a new way for the preparation of higher generation

drugs. Thus, an interdisciplinary field was created - biopharmacy, which combines knowledge

about chemically-defined active substances and their pharmacological properties with the

field of pharmaceutical technology, which deals with the formulation and design of

application forms. Together with the support of the modern knowledge of pharmacodynamics,

pharmacokinetics, chronopharmacology and pathophysiology, biopharmaceutical findings are

reflected in the development and production of drugs with a controlled and directed release.

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The aim of these practical classes from subject Medical Forms and Biopharmacy is to try to

give students some basic information about the rules and techniques used in the field of

prepared dosage forms, both individually and industrially, with an emphasis on practical skills

training for the preparation and evaluation of liquid, semisolid and solid dosage forms in the

laboratory.

These manuscripts are based on the foundation of the Czech language version that extend and

complement with new knowledge and approaches. Emphasis is placed on trying to generalize

the national particularities of the level of European practices, which is closely connected with

the use of nomenclature, according to the European Pharmacopoeia.

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1. Liquid preparations

1.1 Liquid preparations for oral use

Liquid preparations for oral use are usually solutions, emulsions or suspensions containing

one or more active substances in a suitable vehicle; they may, however, consist of liquid

active substances used as such (oral liquids).

Some preparations for oral use are prepared by diluting concentrated liquid preparations, or

from powders or granules for oral solutions and suspensions, or for oral drops and syrups,

using a suitable vehicle.

The vehicle that is chosen for any preparation for oral use is dependant upon the nature of the

active substance(s) and shoud have organoleptic characteristics appropriate to the intended

use of the preparation.

Liquid preparations for oral use may contain suitable antimicrobial preservatives, antioxidants

and other excipients such as agents for dispersing, suspending, thickening, emulsifying,

buffering, wetting, solubilising, stabilising, flavouring, sweetening and for colour, authorised

by the administrative authority.

Emulsions may show evidence of phase separation but are readily redispersed upon shaking.

Suspensions may show sediment, which is readily dispersed upon shaking in order to have a

suspension that remains sufficiently stable to ensure that the correct dose is delivered.

Various categories of preparations:

Oral solutions, emulsions and suspensions.

Powders and granules for oral solutions and suspensions.

Oral drops.

Powders for oral drops.

Syrups.

Powders and granules for syrups.

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Production

For the manufacturing, packaging, storage and distribution of liquid preparations for oral use,

suitable measures must be taken in order to retain their microbial quality; recommendations

on this aspect are provided in the text Microbiological Quality of Pharmaceutical

Preparations (Ph. Eur). In the manufacturing of liquid preparations for oral use contain

dispersed particles, measures are taken to ensure that there is a suitable and controlled particle

size with regard to the intended use.

During development, it must be demonstrated that a nominal content can be withdrawn from

the container for liquid preparations for oral use packaged in single-dose containers.

During the development of a preparation for oral use whose formulation contains an

antimicrobial preservative, the need for and the efficacy of the chosen preservative shall be

demonstrated to the satisfaction of the administrative authority. A suitable test method,

together with a criteria for judging the preservative properties of the formulation are provided

in the text, Efficacy of Antimicrobial Preservation (Ph. Eur).

Tests

Uniformity of dosage units. Solutions, suspensions and emulsions in single-dose containers

comply with the Test for Uniformity of Dosage Units (Ph. Eur) or, where justified and

authorised, with the test for uniformity of content or uniformity of mass shown below. Herbal

drugs and herbal drug preparations present in dosage form are not subject to the provisions of

this paragraph.

Uniformity of content. (Ph. Eur). Unless otherwise prescribed or justified and authorised,

single-dose suspension preparations comply with the following test: After shaking, empty

each container as completely as possible and carry out the test on the individual contents.

They comply with test B for uniformity of content of single-dose preparations.

Uniformity of mass. Single-dose preparations that are solutions or emulsions comply with

the following test: individually weigh the contents of 20 containers, emptied as completely as

possible, and determine the average mass. Not more than 2 of the individual masses may

deviate more than 10 per cent from the average mass and none may deviate more than 20 per

cent.

Dose and uniformity of dose of oral drops. , Introduce, by means of a dropping device, the

number of drops usually prescribed for one dose into a suitable graduated cylinder, or

introduce by means of a measuring device, the usually prescribed quantity. The dropping

speed can not exceed 2 drops per second. Weigh the liquid, repeat the addition, weigh again

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and carry on repeating the additions and weighing until a total of 10 masses are obtained. No

single mass can deviates more than 10 per cent from the average mass. The total of 10 masses

should not differ more than 15 per cent from the nominal mass of 10 doses. If necessary,

measure the total volume of 10 doses. The volume can not differ more than 15 per cent from

the nominal volume of 10 doses.

Uniformity of mass of delivered doses from multidose containers (Ph. Eur). Liquid

preparations for oral use supplied in multidose containers comply with the test. Oral drops are

not subject to the provisions of this test.

Labeling

The label states the name of any added antimicrobial preservative.

Oral solutions, emulsions and suspensions

Definition

Oral solutions, emulsions and suspensions are supplied in single-dose or multidose containers.

Each dose from a multidose container is administered by means of a device suitable for

measuring the prescribed volume. The device is usually a spoon or a cup for volumes of 5 mL

or multiples thereof, or an oral syringe for other volumes.

Powders and granules for oral solutions and suspensions

Definition

Powders and granules for the preparation of oral solutions or suspensions generally conform

to the definitions in the monographs on Oral powders (Ph. Eur) or Granules (Ph. Eur) as

appropriate. They may contain excipients specifically to facilitate dispersion or dissolution,

and to prevent caking.

After dissolution or suspension, they comply with the requirements for oral solutions or oral

suspensions, as appropriate.

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Tests

Uniformity of dosage units. Single-dose powders and single-dose granules comply with the

Test for Uniformity of Dosage Units (Ph. Eur) or, where justified and authorised, with the

tests for uniformity of content and/or uniformity of mass shown below. Herbal drugs and

herbal drug preparations present in dosage form are not subject to the provisions of this

paragraph.

Uniformity of content (Ph. Eur). Unless otherwise prescribed, justified and authorised,

single-dose powders and single-dose granules containing an active substance of less than 2

mg or less than 2 per cent of the total mass, must comply with test B for uniformity of content

of single-dose preparations. If the preparation has more than one active substance, the

requirement applies only to those substances that correspond to the above conditions.

Uniformity of mass (Ph. Eur). Single-dose powders and single-dose granules must comply

with the test for uniformity of mass of single-dose preparations. If the test for uniformity of

content is prescribed for all the active substances, the test for uniformity of mass is not

required.

Labelling

The label must state:

the method of preparation of the solution or suspension,

the conditions and the duration of storage after reconstitution.

Oral drops

Definition

Oral drops are solutions, emulsions or suspensions that are administered in small volumes

such as drops by means of a suitable device.

Labelling

The label states the number of drops per millilitre of preparation or per gram of preparation if

the dose is measured in drops.

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Powders for oral drops

Definition

Powders for the preparation of oral drops generally conform to the definition of Oral powders

(Ph. Eur). They may contain excipients to facilitate dissolution or suspension in the prescribed

liquid, or to prevent caking.

After dissolution or suspension, they must comply with the requirements for oral drops.

Tests

Uniformity of dosage units. Single-dose powders for oral drops must comply with the test

for uniformity of dosage units (Ph. Eur) or, where justified and authorised, with the tests for

uniformity of content and/or uniformity of mass shown below. Herbal drugs and herbal drug

preparations present in dosage form are not subject to the provisions of this paragraph.

Uniformity of content. (Ph. Eur) Unless otherwise prescribed or justified and authorised,

single-dose powders for oral drops containing an active substance of less than 2mg or less

than 2 percent of the total mass, must comply with test B for uniformity of content of single-

dose preparations. If the preparation has more than one active substance, the requirement

applies only to those substances that correspond to the above conditions.

Uniformity of mass. (Ph. Eur). Single-dose powders for oral drops must comply with the test

for uniformity of mass of single-dose preparations. If the test for uniformity of content is

prescribed for all the active substances, the test for uniformity of mass is not required.

Syrups

Definition

Syrups are aqueous preparations characterised by a sweet taste and a viscous consistency.

They may contain sucrose at a concentration of at least 45 percent m/m. The sweet taste can

also be obtained by using other polyols or sweetening agents. Syrups usually contain aromatic

or other flavouring agents. Each dose from a multidose container is administered by means of

a device suitable for measuring the prescribed volume. The device is usually a spoon or a cup

for volumes of 5 mL or multiples thereof.

Labelling

The label must state the name and concentration of the polyol or sweetening agent.

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Powders and granules for syrups

Definition - Powders and granules for syrups generally conform to the definitions in the

monograph on Oral powders (Ph. Eur) or Granules (Ph. Eur). They may contain excipients to

facilitate dissolution. After dissolution, they must comply with the requirements for syrups.

Tests

Uniformity of dosage units. Single-dose powders and granules for syrups must comply with

the test for uniformity of dosage units (Ph. Eur) or, where justified and authorised, with the

tests for uniformity of content and/or uniformity of mass shown below. Herbal drugs and

herbal drug preparations present in dosage form are not subject to the provisions of this

paragraph.

Uniformity of content (Ph. Eur). Unless otherwise prescribed, justified and authorised,

single-dose powders and granules for syrups containing an active substance of less than 2 mg

or less than 2 per cent of the total mass comply with test B for uniformity of content of single-

dose preparations. If the preparation has more than one active substance, the requirement

applies only to those substances that correspond to the above conditions.

Uniformity of mass (Ph. Eur). Single-dose powders and granules for syrups must comply

with the test for uniformity of mass of single-dose preparations. If the test for uniformity of

content is prescribed for all the active substances, the test for uniformity of mass is not

required.

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1.2 Liquid preparations for cutaneous application

Liquid preparations for cutaneous application are preparations consisting of a variety of

viscosities intended for the local or transdermal delivery of active ingredients. They are

solutions, emulsions or suspensions that may contain one or more active substances in a

suitable vehicle. They may contain suitable antimicrobial preservatives, antioxidants and

other excipients such as stabilisers, emulsifiers and thickeners.

Emulsions may show evidence of phase separation, but are readily redispersed upon shaking.

Suspensions may contain sediment that is readily dispersed upon shaking to produce a

suspension that is sufficiently stable to enable a homogeneous preparation to be delivered.

Where applicable, containers for liquid preparations for a cutaneous application must comply

with the requirements of Materials used for the manufacture of containers (Ph. Eur.) and

Containers (Ph. Eur.).

When liquid preparations for cutaneous applications are dispensed in pressurised containers,

the containers must comply with the requirements of the monograph on Pressurised

pharmaceutical preparations (Ph. Eur.).

Preparations specifically intended for use on severely injured skin must be sterile.

There are several categories of liquid preparations for cutaneous application. For example:

Shampoos,

Cutaneous foams.

Production

During development, it must be demonstrated that a nominal content can be withdrawn from

the container of liquid preparation for cutaneous application presented in single-dose

containers.

In the manufacturing of liquid preparations for cutaneous application which contains

dispersed particles, measures must be taken to ensure a suitable and controlled particle size

with regard to the intended use.

In the manufacturing, packaging, storage and distribution of liquid preparations for cutaneous

application, suitable measures must also be taken to ensure their microbial quality.

Recommendations on this aspect are provided in the text Microbiological quality of

pharmaceutical preparations (Ph. Eur).

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Sterile liquid preparations for cutaneous application are prepared using materials and methods

designed to ensure sterility and to avoid the introduction of contaminants and the growth of

micro-organisms. Recommendations on this aspect are provided in the text Methods of

preparation of sterile products (Ph. Eur).

During the development of liquid preparations intended for cutaneous application whose

formulation contains an antimicrobial preservative, the need for and the efficacy of the chosen

preservative shall be demonstrated to the satisfaction of the administrative authority. A

suitable test method, together with criteria for judging the preservative properties of the

formulation are provided in the text Efficacy of antimicrobial preservation (Ph. Eur).

Tests

Sterility (Ph. Eur). Where the label indicates that the preparation is sterile, it has complied

with the test for sterility.

Storage

If the preparation is sterile, it must be stored in a sterile, airtight, tamper-proof container.

Labelling

The label must state:

The name of any added antimicrobial preservative;

Where applicable, that the preparation is sterile.

Shampoos

Definition

Shampoos are liquid, or occasionally, semi-solid preparations intended for application to the

scalp and the subsequent rinsing with water. When rubbed with water they usually form a

lather.

They can be emulsions, suspensions or solutions. Shampoos normally contain surface active

agents.

Cutaneous foams

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1.3 Pharmaceutical solutions

Solutions are some of the oldest dosage forms used in the treatment of patients, and the

compounding of solutions retains an important place in therapeutics at the present.

Solutions can be defined as a homogenous one-phase system consisting of two or more

components:

Solvent (dispersing compound) - determines the phase of the solution and usually constitutes

the largest proportion of the system, but there are some exceptions, such as syrups.

Solute (dissolved compound) - dispersed as molecules or ions throughout the solvent; i.e. they

are considered to be dissolved in the solvent.

Solutions may exist in any phase, but from a pharmaceutical standpoint, there are liquid

formulations that contain one or more chemical substances dissolved in a suitable solvent or

mixture of mutually miscible solvents. Generally, water is chosen as the vehicle in which

active ingredients (APIs) are dissolved because it is non-toxic, non-irritant, tasteless,

relatively cheap and many substances are water-soluble. In cases where drugs are not

particularly water-soluble or suffer from hydrolysis in an aqueous medium, other solvents are

used (hydrophilic - ethanol, glycerol, propylenglycol, PEG; hydrophobic - liquid paraffin,

natural and synthetic oils, ether, chloroform, benzene). Solutions can also contain other

excipients, such as solubilizators, antimicrobial agents (preservatives), antioxidants, buffers

and isotonicity modifiers, emulsifiers, viscosity increasing agents (thickeners), flavouring

agents, colours and perfumes, and absorption enhancers.

Solutions are popular due to their simplicity and the speed of their preparation, along with

many other advantages.

Advantages of solutions

Easy to dose from concentrate by simple dilution

Easy to mix if necessary

Easy to measure accurately

Easy to administer orally (acceptable for paediatric and geriatric use)

Administration by any route

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More quickly effective than tablets and capsules (fast therapeutic response)

Homogenous (give uniform dose)

Reduce irritation to the gastric mucosa

Disadvantages

Less stable than solid dosage forms

Bulky, therefore difficult to transport

Solubility may be limited

Need to mask taste or odours (oral)

Need an accurate spoon to measure the dose

Fragile packaging

Microbial contamination is more likely

Solubility

Solubility is defined as the rate of dissolution of solids in liquid (for liquid ingredients it is a

measure of their mutual miscibility). This value could be quantitatively expressed as the

concentration of a saturated solution at a certain temperature (pharmacopoeias characterize

the solubility usually by words i.e. very soluble – practicaly insoluble). Solubility depends on

temperature, pressure, the nature of the solutes and solvents (similia similibus solventur), the

pH of the solution, the presence of common ions and the presence of other excipients

(electrolytes, solubilizators, etc.).

Solubility can be improved by physical or chemical means:

Physical solubility improvement (used as processing step in pharmaceutical

technology):

o Co-solvents: non-aqueous solvents miscible with water, having a lower surface

tension than water (eg. ethanol, glycerol, propylene glycol).

o Complexation: two basic procedures (using cyclodextrines – molecular

inclusions or poly-iodine complexes creation) are used.

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o Hydrotropism: distress of the associated water structure by extensive ions

(sodium benzoate, sodium acetate, etc.).

o Micellar solubilization: solubilized substance enters the colloidal micelles of

surfactants.

Chemical solubility improvement (chemical modification of active substance):

o Creating more soluble salts

o Creating prodrugs: the preparation of inactive compounds (with better physico-

chemical properties) that must undergo biotransformation (bioactivation) in the

body (enzymatic x non-enzymatic) in order to have therapeutical activity

According to the pharmacopoiea the solutions could be used both topically and systemically.

Classification of pharmaceutical solutions

Sterile solutions

o Parenterals (injections, infusions)

o Eye – ocular – ophthalmic (drops, rinses)

o Solutions designed for wounds, seriously damaged skin and mucous membrane

administration

o Solutions for peritoneal dialysis, irrigation of body cavities and surfaces of

open wounds (e.g. surgical operations)

Solutions for local administration (topical) and for the administration into the

respiratory tract

o Nose and ear instilations, drops, sprayes, rinses

o Dermal solutions – liquida cutanea

Medicinal solutions

Aromatic waters and spirits

Mucilages

Shampoos

Collodions

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Douches

Oral and vaginal solutions

o Oral – oromucosalia

Gargles – gargarismatae

Oral rinses, mouthwashes – aquae gingivales

Solutions for gum treatment – solutiones gingivales

Oral solutions – solutiones oromucosales

o Vaginal

Peroral and rectal solutions

o Peroral

Medicinal solutions (also in the form of drops)

Aromatic waters and spirits

Syrups

Mucilages (gels)

Elixirs

o Rectal

Preparations for cleansing, diagnosis or therapeutic reasons (enemas)

General methods of preparation

There are 4 basic possibilities for preparing pharmaceutical solutions:

1. Dissolving at a normal (laboratory) temperature.

2. Dissolving at a higher temperature.

3. Dissolving by using substances for improving solubility.

4. Preparing by chemical reaction.

Packaging

Packaging is specific for each type of preparation and administration route.

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Usually small bottles are used, with or without a dropper, made from various material (glass –

heavy, innert; plastic – PVC, PE), either coloured (photosensitive substances) or transparent.

Labels

Basic labels

o Colour (white – peroral, injection; red – oral, topical; yellow – laboratory

reagents)

o Label requirements (information for patient, dosage, date, adress of pharmacy,

signature, expiration, amount)

Additional labels - important notices

Corrosive! Flammable! Shake before use! Only for animals! Poison!

Storing conditions (Keep away from light!; Keep in cold!)

Shelf life

Specifies the pharmacist with respect to:

o National authorities’ recomandations

o Scientific literature

o Physico-chemical and microbiological stability

o Duration of therapy

For the most of the prepared pharmaceutical solutions, the maximum shelf life is 1 month if

protected antimicrobially (preservatives) or prepared from non-aqueous solvents,

and only 1 week for a antimicrobially non-protected water solution (2 weeks if stored in cold

conditions).

1. Dissolving at a normal (laboratory) temperature

a) Dissolution of active ingredients in adequate amounts of the specified solvent.

b) Solution mixing.

c) Filtration.

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If there is more than 1 substance in the prescription to be dissolved, each substance should be

dissolved in a separate amount of the solvent, and the partial solutions should be mixed.

If there are more solvents in prescription, each substance should be dissolved in a solvent in

which it is best soluble, and the partial solutions should be mixed.

Volatile substances or liquids must be added at the end of the process.

EXAMPLES

Exercise 1.3.1

Ammoniae solutio 10% - Ammonia solution 10%

Ammoniae solutio concentrata 19.25

Aqua purificata 30.75

Preparation procedure: Mix both liquids together and filtrate, while working in the fume hood

(ammonia vapors are irritating).

Additional labels on package: Corrosive!

Storage conditions: Store at temperature < 20°C

Exercise 1.3.2

Calcii chloridi solutio – Calcium chloride solution

Calcii chloridum hexahydricum 25.0


Preparation procedure: Dissolve calcium chloride in purified water; mix and filtrate the blend.

Exercise 1.3.3

Camphorae spiritus – Camphorated alcohol

Camphora racemica 2.50 Ethanolum 96% (V/V) 14.25


Preparation procedure: Dissolve camphor in ethanol. Add water gradually. Filtrate the

solution.

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Additional labels on package: Flammable!

Storage conditions: Cold area (8-15°C), Keep away from light!

Shelf life: 3 months

Notes: Preparations with acontent of ethanol 40% can be marked as „Flammable!“

Preparations with content of ethanol higher than 60% or with content of ether in any

concentration must be labeled as „Flammable!“.

Preparations containing more than 20% of ethanol or other non-water solvents are

antimicrobialy protected (prolonged shelf life).

Exercise 1.3.4

Solutio Castellani sine fuchsino – Castellani solution without fuchsin

Acidum boricum 0.8 Phenolum 3.6 Resorcinolum 8.0 Acetonum 4.0 Ethanolum 96% 7.4


Preparation procedure: Dissolve phenol and resorcinol in a mixture of ethanol and acetone.

Add a water solution of boric acid and filtrate the solution.

Storage conditions: Keep away from light!

Do not issue without a prescription!

Notes: Crystalline phenol may be replaced by liquid phenol (Phenolum liquefactum)

110 g liquid phenol = 100 g phenol + 10 g H2O

If the preparation contains photosensitive substance, the product must be kept in a dark

(brown) glass bottle.

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Exercise 1.3.5

Solutio Fraeser – Fraeser‘s solution

Acidum benzoicum 1.35 Acidum salicylicum 1.35 Iodi solutio ethanolica 6.75

Camphorae spiritus 40.55

Preparation procedure: Dissolve benzoic and salicylic acid in camphorated alcohol. Add an

ethanolic iodine solution.

Additional labels on package: Flammable!, Keep away from light!

Storage conditions: The product must be kept in dark (brown) glass bottle so as not to react

with the iodine.

Exercise 1.3.6

Solutio Galli-Valerio - Galli-Valerio solution

Phenolum 0.5 Glycerolum 85% 1.5 Natrii tetraboras decahydricus 1.5 Formaldehydi solutio 35% 2.5

Aqua purificata ad 100.0

Preparation procedure: Dissolve sodium tetraborate in approximately 90g of purified water.

Add glycerol, a formaldehyde solution and phenol (liquid phenol). Add the rest of water up to

100g. Mix the blend and filtrate the solution.

Additional labels on package: Keep away from light!

Notes: Crystalline phenol could be replaced by liquid phenol (Phenolum liquefactum).

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Exercise 1.3.7

Spiritus ethereus – Ether alcohol (= Guttae Hoffmani)

Ether solvens 6.25

Ethanolum 85% 18.75

Preparation procedure: Mix ether with ethanol.

Additional labels on package: Flammable!

Storage conditions: The product must be kept in dark bottle at a temperature between 8 and

15°C.

Exercise 1.3.8

Rp.

Kalii iodidi 2.5 Aquae purificatae ad 100.0 M.f.sol.

D.S. 3 x 1 spoonful

Preparation procedure: Dissolve potassium iodide in water. Filtrate the solution.

Exercise 1.3.9

Rp.

Tannini 1.0 Aquae purificatae ad 100.0 M.f.sol.

D.S. Linning.

Preparation procedure: Dissolve tannin in water.

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Exercise 1.3.10

Rp.

Argenti nitratis 0.1 Aquae purificatae ad 10.0 M.f.sol. D.S. Dotting of the base of the leg ulcers

Sub signo veneni! Ad manus medici!

Preparation procedure: Dissolve silver nitrate in water. Filtrate the solution.

Notes: Silver nitrate is a photosensitive substance. Silver ions show a great willingness to be

reduced to metallic silver-black, so if the silver nitrate contaminates your clothing or skin it

can result in bad staining.

2. Dissolving at a higher temperature

a) Addition of API to the warmed solvent.

b) The dissolving of API by continual mixing or by quick boiling in water bath or cooker.

c) Supplement of evaporating solvent. Filtration of cooled solution.

If there are substances in formulas which do not need higher temperatures for dissolving, they

should be added to the cooled solution at the end of the preparation process or they should be

dissolved in part of the solvent at a normal temperature.

Volatile or thermolabile substances must be added at the end of the process to a cooled

solution.

Volatile solvents must be warmed in a water bath, not in a cooker or a fire!

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EXAMPLES

Exercise 1.3.11

Acidi borici solutio 3% - Solution of 3% boric acid

Acidum boricum 3.0


Preparation procedure: Dissolve boric acid in water heated to 60-70°C. Filtrate the solution.

Storage conditions: The product must be kept at a temperature between 8 and 15°C.

Exercise 1.3.12

Aqua conservans – Preservation water

Methylparabenum 0.067 Propylparabenum 0.033


Preparation procedure: Dissolve the prescribed amount of methyl- and propylparaben

(analytical balances) in boiling water. Boil for 10 minutes. Supplement the evaporated water

after cooling. Filtrate the solution.


Notes: Addition of Aq. conservans to preparation is necessary to market on the label by c.p.

abbreviation (presence of parabens).

Exercise 1.3.13

Natrii tetraboratis solutio glycerolica – Glycerolic solution of sodium tetraborate

Natrii tetraboratis 5.0

Glycerolum 85% 45.0

Preparation procedure: Dissolve sodium tetraborate in glycerol in a close-neck bottle by

heating on water bath.

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Exercise 1.3.14

Solutio Jarisch – Solution of Jarisch

Acidum boricum 2.0 Glycerolum 85% 4.0


Preparation procedure: Dissolve boric acid in boiling purified water. Add glycerol after

cooling. Supplement the evaporated water. Filtrate the solution.

Shelf life: 1 month (parabens – microbiologicaly stable)

Notes: Addition of Aq. conservans must be market on the label by c.p. abbreviation

(presence of parabens).

Exercise 1.3.15

Rp.

Ethacridinii lactatis 1.0 Aquae purificatae ad 100.0 M.f.sol.

D.S.: 1 spoonful into a glass of water for lavage of the oral cavity.

Preparation procedure: Dissolve ethacridine lactate at a high temperature (water bath) in

purified water by continual mixing until the solution turns yellow.

Shelf life: 3 weeks


26

3. Dissolving by using substances that improve solubility

The basic preparation procedure consists of mixing API with a substance that improves

solubility immediately before dissolving, or dissolving API in solution of solvent and a

substance which improves solubility.

EXAMPLES

Exercise 1.3.16

Iodi solutio aquosa – Water iodine solution

Iodum 1.0 Kalii iodidum 2.5


Preparation procedure: Dissolve potassium iodide (excipient) in 2.5g of purified water to get a

50% KI solution. Dissolve 1.0g of iodine (API) in a KI solution. Add water up to 100.0g.

Storage conditions: The product must be kept in a dark (brown) glass bottle which does not

react with iodine.

Exercise 1.3.17

Iodi solutio glycerolica - Glycerolic iodine solution

Iodum 0.25 Kalii iodidum 2.50 Aqua purificata 2.50

Glycerolum 85% 19.75

Preparation procedure: Dissolve potassium iodide (excipient) in purified water to get a 50%

KI solution. Dissolve 0.25g of iodine (API) in a KI solution. Add glycerol up to 25.0g. Filtrate

the solution.

Storage conditions: The product must be kept in a dark (brown) glass bottle that does not react

with iodine.

27

Exercise 1.3.18

Iodi solutio ethanolica - Ethanolic iodine solution

Iodum 1.3 Kalii iodidum 0.5 Aqua purificata 1.7

Ethanolum 96% 16.5

Preparation procedure: Dissolve potassium iodide (excipient) in purified water to get a

concentrated KI solution. Ad 1.3g of iodine (API) to the KI solution. Add ethanol up to 20.0g.

Filtrate the solution.

Storage conditions: The product must be kept in adark (brown) glass bottle that does not react

with iodine.

Additional label: Flammable!

Exercise 1.3.19

Rp.

Mentholi 0.1 Ethanoli 96% 1.0 Polysorbati 80 1.0 Aquae purificatae ad 100.0 M.f.sol.

D.S. Liniment.

Preparation procedure: Dissolve menthol in ethanol (co-solvent). Mix with polysorbate

(surfactant) in mortar. Add water. Filtrate the solution.

4. Preparing by chemical reaction

There is a defined specific procedure for each preparation.

28

EXAMPLES

Exercise 1.3.20

Calcii hydroxidi solutio – Solution of calcium hydroxide

Calcii oxidum 1.0

Aqua purificata q.s.

Preparation procedure: Sprinkle crushed calcium oxide in a ceramic bowl with approximately

4ml of boiled, purified water. Pour the resulting suspension into a bottle (100ml bottle of clear

glass), add 50ml of purified water, shake it vigorously and allow it to stand for approximately

1 hour. Decante the clear supernatant, remain in the bottle only solid calcium hydroxide and

fill it by 100ml of water, thoroughly shake the bottle and close it. Decante the fluid above the

supernatant without shaking just before use.

Storage conditions: The product should be stored in a completely filled and sealed container

resistant to alkalies.

Notes: Freshly boiled purified water (free of carbon dioxide) must be used for the preparation.

The preparation must be stored with the precipitate to provide a useful consistant

concentration of calcium hydroxide in the solution.

Exercise 1.3.21

Spiritus saponis kalini – Alcohol with potassium soap

Kalii hydroxidum 2.00 Lini oleum 8.75 Ethanolum 96% 7.50 Aqua purificata 6.50

Lavandulae etheroleum 0.25

Preparation procedure: Dissolve potassium hydroxide in 3 ml of purified water. Add linseed

oil and 2.5g of ethanolu to 96%. Close the mixture in a short-neck bottle, shake it until

complete clarification or a thickening of the fluid is achieved. Add the rest of water and

lavender essential oil solution to the ethanol

Storage conditions: The product should be stored in well sealed bottles that are protected from

light.

29

1.4 Syrups

Syrups are concentrated solutions of sugars or polyhydric alcohols in water, in extracts of

herbal drugs or in fruit juices and are intended for internal use. From the sugars the sucrose or

glucose, fructose and invert sugar are used. From polyhydric alcohols - polyols (mannitol,

sorbitol) are used. According to Pharmacopeia, the syrups are drug forms with viscous

consistency, a sweet taste, and contains water.

Excipients

Sweetness is achieved by the use of sucrose (at least 45 % of total weight), polyols,

polyhydric alcohols or artificial sweeteners. Syrups are usually used for masking taste, but

may have a therapeutic effect if they contain drugs or are prepared by dissolving the sugars in

extracts of herbal drugs. With the exception of simple syrup, they usually contain a number of

auxiliary substances (e. g. antimicrobial substances, flavors, fragrances and dyes).

General methods of syrups preparation

1. By dissolving sucrose or sugar alcohol at an higher or room temperature:

• in water

• in aqueous solutions of active ingredients and excipients

• in extracts of herbal drugs

2. Adding (dissolving) drugs, tinctures, extracts, etc. to the simple syrup.

Ad 1. Most syrups are prepared at elevated temperatures using a uniform procedure,

which can be divided into several steps:

• Sucrose and water/liquids are weighed: the ratio of these components is in most

Pharmacopoeias 64:36

• The sucrose is dissolved by stirring while heating (usually up to 80°C) over the

water bath or the sucrose is placed into a pre-heated liquid where it is dissolved

without heating

• Welding solution and defoaming: after the dissolution of sucrose, the syrup,

without stirring, is quickly cooked. Do not cook unless sucrose is completely

30

dissolved. The foam that forms containing coagulated proteins or ballast

substances is collected and removed.

• Adjustment to the prescribed density: the evaporated liquid is replenished to

the prescribed quantity by freshly boiled water.

• Filtration and rippling - hot syrups are filtered with a suitable filter. If there are

non-filterable and sedimenting particles present, then rippling may be used

• Filling – the still hot syrup is poured into sterilized bottles up to the neck. After

cooling, the condensed vapor is admixed with the syrup while it is being

shaken.

Ad 2. Preparation at room temperature takes place simply by dissolving sucrose in

water or other liquids with frequent stirring or shaking. An alternate method would be to fill a

percolator with sucrose and dissolve it at a slow rate with solvent.

Packaging

Syrups are stored in glass bottles under cool conditions (8-15°C), which prevent the

microorganisms from multiplying. For the same reason, various syrups are preserved by the

addition of antimicrobial preservatives (parabens, sodium benzoate, sorbic acid, etc.).

Selected pharmacopoeial syrups: Syrupus altheae, Syrupus plantaginis, Syrupus simplex.

EXAMPLES

Exercise 1.4.1

Syrupus simplex

Saccharosum 64.0


Preparation procedure: Sucrose is stirred into and dissolved in purified water heated to about

80°C and then is briefly cooked. The foam is removed and hot freshly boiled purified water is

added to the syrup to get 100g. If necessary, the still hot solution is filtered through a suitable

filter and filled to dry (and if necessary sterilized) containers up to the neck. Containers must

be immediately closed. The syrup is stored in a completely filled container, protected from

light, at temperature of 8°C to 15°C.

31

Exercise 1.4.2

Syrupus altheae

Altheae radix 2.5 Ethanolum 96% 2.0 Aqua purificata 40.0 Saccharosum 64.0

Methylparabenum 0.15

Preparation procedure: Radix altheae is washed with purified water at room temperature and

then placed into a glass, porcelain or enamel container. A mixture of 1g of ethanol 96% (V/V)

and 40g of purified water is then added. Stirr occasionally, and let it macerate for 2 hours at

room temperature. The extract is then filtered through a suitable filter. The drug must not be

pushed or pressed. The drug is only washed with purified water, until the required weight of

36g is achieved. Then 1g of ethanolic solution of methyl paraben is added. Sucrose is added

and the next procedure is the same as the preparation of syrupus simplex. Syrup is stored in a

completely filled container, protected from light, at a temperature of 8°C to 15°C.

Exercise 1.4.3

Syrupus plantaginis

Plantaginis folium 5.0 Agua purificat 45.0 Saccharosum 64.0 Methylparabenum 0.15

Ethanolum 96% 1.0

Preparation procedure: Foilum plantaginis is placed into a glass or porcelain vessel, and

boiling purified water is poured over it. The vessel is tightly sealed and left to stand for 2

hours with occasional stirring. After this, the obtained liquid is filtered through a suitable

filter. The drug is then immediately pressed and the obtained extract is also filtered. These

two filtrates are then mixed, and the pressed drug is washed by purified water. This mixture of

filtrates is then refilled using this water to achieve the required weight of 36g, then 1g of

ethanol solution of methyl paraben is added. Sucrose is added and the next procedure is the

same as for the preparation of syrupus simplex. The syrup is then stored in a completely filled

container, protected from light, at a temperature from 8°C to 15°C.

32

1.5 Aromatic waters

Aromatic waters are saturated aqueous solutions of easily volatile substances, such as

essential oils. They are used mostly as taste or smell maskers, but some may also have a

moderate therapeutic effect (e.g. Aqua carminativa). For preparation, explanation of

properties and interpretation of some incompatibilities, it is important to emphasize that

aromatic waters are saturated water solutions. Because they are therefore sensitive to

temperature, they have to be kept at a temperature than during their preparation because it

would otherwise become cloudy.

The aromatic waters were originally prepared by distilling fresh or dried plant drugs with hot-

water steam. This preparation is now considered to be old-fashion. The basic method remains

the preparation of dissolving oils or other easily volatile substances in water.

Excipients

Various auxiliary substances (alcohol, talc) are added for the facilitation of the preparation

and for quality improvement. Even so, the classic preparation of aromatic waters is quite

lengthy: a mixture of essential oils, ethanol and water must be intensively shaken for a long

period of time in order to achieve a saturated state.

General method of preparation

Aromatic waters may be also prepared from essential oils. In this way, these oils may be

solubilized with hydrophilic surfactants (e. g. polysorbate 80). The advantage is the speed of

preparation; the drawback is the taste and odor of polysorbate, which can often distort the

qualitative features of the product.

The general formula for the preparation of aromatic waters:

Etheroleum 0.1 Ethanolum 96% 1.0 Aqua purificata 98.9

Talcum 0.5

Note: The amount of essential oil and ethanol may vary according to the type of prescription.

Essential oils are dissolved in ethanol 96%. Purified water is added to this solution while

under a constant strong shaking and then is shaken for another 15 min. About 2g of this

33

solution is thoroughly mixed with 0.5g of talc and added back to the main portion of the

liquid. After an intensive mixing the solution is left to stand, and is then passed through a

filter moistened with purified water.

Aromatic waters have limited stability; they are easily attacked by microbes, and therefore

should be prepared only when needed. In the pharmacy it is beneficial to prepare concentrated

aromatic water in advance. Concentrated aromatic water is a 40-50% ethanolic solution of

etheroleum. This concentration is achieved by the dilution of a concentrated ethanolic solution

of etheroleum and water.

Terpenic hydrocarbons without odor are eliminated in the form of turbidity, which is removed

by filtration using talc as a sorbent. A higher proportion of ethanol has a stabilizing role - it

protects the product against microbial attack. The desired aromatic water is prepared from the

stock solution by diluting purified water at a ratio of 2 : 98 when needed.

Selected aromatic pharmacopoeial waters: Aqua carminative, Aqua carminativa rubra,

Spiritus anisi compositus (this is basically the concentrated form of aromatic water).

EXAMPLES

Representative’s pharmacopoeial aromatic plants

Exercise 1.5.1

Aqua carminativa

Carvi etheroleum citri etheroleum 0.01 Citri oleum 0.01 Citronellae etheroleum 0.01 Coriandri etheroleum 0.01 Foeniculi etheroleum 0.01 Menthae piperitae etheroleum 0.24 (12 drops) Ethanolum 96% 0.50 Talcum 0.50


Preparation procedure: Preparation should be according to the general procedure for aromatic

water (see above), e.g., stored in a completely filled container and protected from light.

34

Exercise 1.5.2

Anisi spiritus compositus

Anisi eteroleum 2.0 Ammonii chloridum 3.0 Ethanolum 96% 40.0


Preparation procedure: Eteroleum anisi is dissolved in ethanol 96% with constant shaking;

then purified water and ammonium chloride are added. If the liquid is turbid, add 3g talc,

shake, and leave it to stand for a few hours with occasional stirring and then filter it. Store

where it will be protected from light.

Further examples of aromatic waters

Exercise 1.5.3

Aqua mentehae piperitae

Menthae piperitae etheroleum 0.1 Ethanolum 96% 1.0 Aqua purificata 98.9

Talcum 0.5

Preparation procedure: It is prepared according to procedure for aromatic waters.

Exercise 1.5.4

Aqua mentehae concentratae

Menthae piperitae etheroleum 1.8 Ethanolum 96% q.s. Aqua purificata 58.2

Talcum 3.0

Preparation procedure: Menthae piperitae etheroleum is dissolved in 40g of ethanol 96%, and

under constant shaking is diluted with purified water. Shake for 15 minutes and leave to stand

for 24 hours at room temperature. Then mix about 10g of this mixture with 3g of talc, shake

thoroughly, and add it back to the main portion of the liquid. After shaking, this mixture is left

to settle and then passed through a dry filter. To this filtrate is added 2 % of ethanol 96%. This

35

addition of ethanol prevents the formation of turbidity in case the temperature falls during

storage.

36

1.6 Mucilages

Mucilages are formed from swelling expanding polymeric substances. They can be natural,

semisynthetic or synthetic. Viscous colloidal solutions or dispersions are created by the

swelling of these substances in water (or different hydrophilic solvents).

Excipients

Substances which allow the creation of mucilage are usually able to transform themselves

from a "sol" to a "gel" form. The transformation from "sol" to "gel" is performed with higher

concentrations of polymeric substances during changes of temperature, a change of pH, or

from being in the presence of certain ions. These substances are often considered to be "gel-

creating".

It is not always easy to say whether a product belongs to a group of mucilages or gels. From a

theoretical point of view, mucilage is the colloidal system in a state of "sol". From a practical

point of view the mucilage is considered to be a polymeric solution (dispersion) having the

characteristics of a viscous liquid.

Method of preparation

The preparation of gels and mucilages is not uniform, since different substances require

different conditions for swelling, dissolution and/or gelation (sol-gel transition). It is generally

prepared by placing a uniform, finelyp-ulverized gelling agent on the surface of a liquid,

usually at room temperature. The premix of the gelling agents with alcohol or glycerol is

sometimes recommended for substances that form clumps easily, or for substances having

trouble with expansion.

Processes of swelling

1. Spontaneous swelling at room temperature (Accacia, MC).

2. Swelling at higher temperature (CMC, agar).

3. Swelling at room temperature, followed by heating Gelatine, starch.

4. Dispersal at higher temperature, followed by swelling during cooling

HPMC, starch.

5. Neutralization of swollen dispersion (Carbomers).

37

EXAMPLES Selected Pharmacopoeial mucilages

Exercise 1.6.1

Mucilago accaciae

Accaciae gummi dispersion desiccatum (Accaciae gummi) 10.0

Aqua conservans ad 30.0

Preparation procedure: Pulverized arabic gum is dissolved in Aqua conservans. If necessary,

it is filtered and bottled. It is stored in containers protected from light, at a temperature

ranging from 8°C to 15°C.

Exercise 1.6.2

Mucilago methylcellulosi

Methylcellulosum 2.5 Glycerolum 85% 10.0


Preparation procedure: Methyl cellulose is dispersed in about 40ml of purified water and left

to stand for 15 minutes. The expanded mixture is stirred until smooth. The rest of the

remaining mixture of glycerol and purified water is then added and stirred into the transparent

slime. It is stored in containers protected from light, at a temperature ranging from 8°C to

15°C.

38

Other mucilages

Exercise 1.6.3

Carmellosi natrici mucilago

Carmellosum sodium 2.0 Glycerolum 85% 10.0

Aqua conservans ad 100.0

Preparation procedure: A mixture of Aq. conservans and glycerol is heated to approximately

85°C; while constantly stirring, sodium carmellose is added. After dissolving, evaporated

water is added. The mixture is then stirred further.

Exercise 1.6.4

Mucilago methylcellulosi

Methyl cellulosum 1.0


Preparation procedure: Approximately the half the amount of purified water is heated to 80°C

and is poured into a melamine mortar blender. Methyl cellulose is spread on the water surface

and left to swell for 15 minutes. The rest of the water is cooled to a temperature of about 0°C.

Cold water or ice drift is put into the swollen methyl cellulose and stirred into the

homogenous, transparent mucilage.

Note: In addition to the above mentioned or pharmacopoeial procedure (see above, Exercise

1.6.2), methyl cellulose mucilage can be prepared by another simple, but lengthy method. The

methyl cellulose is left to swell at room temperature for at least 12 hours, but usually for

overnight.

39

1.7 Herbal drug preparations

Products obtained by extraction methods are primarily fluid extracts from plants. There are

infusions, decoctions, tinctures and extracts that are traditional pharmacopoeial and

pharmaceutical forms.

Active ingredients

They contain a mixture of active, side and ballast substances. The extracts are composed of

the substances with different physical and chemical properties, varying stability and solubility

and therapeutic values.

Therefore, some types of extracts, like stable dried extract, are preferred more in recent years.

Dried extracts ensure a stable content of active substances, mixtures without admixtures, or

they contain purified active pharmaceutical ingredients.

Extractive methods are divided according to their course: they can be periodic, semi-continual

and continual.

Methods of preparation

1. Periodic extraction methods - maceration. Ingredients are extracted from drugs to

a solvent in a closed system. This means that the drug and the solvent is placed

together in a container. After a certain period of time, the extract and the residual

plant remains. Maceration can take place under different temperatures, in one step

or in several, and with a different velocity of movement between solvent and drug.

Maceration is used for the preparation of infusions, decoctions, tinctures an

extracts.

2. Semi-continuous extraction methods - percolations. Drug is loaded into a

container and the in-flow and out-flow of the solvent are continuous. Percolations

take place at room temperature, either in one or in the series of percolators.

Percolation is used for the preparation of tinctures an extracts.

3. Continuous extraction methods. Continuous extraction methods are

characterized by utilizing a continuous supply of drug and fluid with a continuous

separation of solvent and residual of drugs. These methods require special

production equipment used in pharmaceutical production.

40

General requiremets in the preparation of extracts (infusions, decoctions, tinctures, extracts)

from herbal drugs and methods of extractions:

Unless otherwise prescribed, the following parts of flowers are used for preparation:

finely cut and very finely cut flowers, leaves, pulps, stems and roots, and coarsely

powdered fruits and seeds.

If the amount of drug is not prescribed, the preparation of the infusions is performed in

ratio: for 10g of drug 100g extract is prepared. In the case of mucilage drugs, for 10g

of the drug, 200g of extract is prepared.

For the preparation of tinctures of potent and highly potent drugs, 10g of the drug is

used for the preparation of 100g of tincture. In other cases, 20g of drug is used for the

preparation of 100g of tincture.

Suitable adjuvants increasing extraction methods and stabilizing agents can be used

according to the nature of the drug.

For drugs containing alkaloids, an acidifying agent such as citric acid is added.

According to the quantitative content of alkaloids it is used in the form of a pre-

wetting mixture; e.g., for 1g of radix with a content of 0.02g of alcaloids, 0.02g of

citric acid is used. The extraction of saponine and mucilage drugs is better performed

in a slightly alkaline environment. Prescribed drugs are added to the finished extract.

These are aqueous extracts, which are usually prepared at the time needed (ex tempore).

Maceration methods take place at room temperature or higher, by dissolving dried extracts,

and by diluting concentrated extracts.


1. Preparation at room temperature

Infusions of drugs containing a mucilage substance: The drug is macerated with water at room

temperature for 30 minutes, and stirred occasionally. The mucilage, obtained without

pressing, is filtered, and the filter is washed with an adequate amount of the solvent so that the

prescribed quantity of the product can be received.

41

2. Preparation at higher temperature

Extracts which are prepared at higher temperatures are called decoctions and infusions. The

drug is placed in a porcelain mortar blender and kneaded with water three to five times the

quantity, until it is evenly wetted and left to stand for 15 min. The drug is then placed into a

suitable container and capped. Depending on whether the infusion or decoction is being

prepared, proceed is follows:

For the infusions: The drug is mixed with the remaining boiling water, placed over a

boiling water bath for 5 minutes, stirring occasionally. The container is kept for 45

minutes at room temperature while occasionally being stirred. The extract is filtered,

pressed out, and then the container is refilled up to the required quantity of product

with water, which was used for washing the filter.

For the decoctions: The drug is mixed with the remaining boiling water, placed over

a boiling water bath for 30 minutes, stirring occasionally. The extract is filtered while

still hot, pressed out and the container is refilled up to the required quantity with

water, which was used for washing the filter.

3. Maceroinfusion

Extraction is initially taken place at room temperature and then at a temperature continually

decreasing from 60-70°C down to room temperature: The drug is then put in with half of the

amount of solvent, mixed, and left to infuse for 15 minutes. The other half of the boiling

solvent is then added to the mixture, and left to stand for 15 minutes.

42

EXAMPLES Preparation at room temperature

Exercise 1.7.1

Rp.

Althaeae radicis infusi 5.0 : 100.0

D.S. 3 x1 spoonful

Exercise 1.7.2

Rp.

Lini seminis infusion 5.0 : 100.0

D.S. 1 spoonful several times a day

Preparation at higher temperatures

Exercise 1.7.3

Rp.

Quercus corticis decocti 5.0 : 100.0

D.S. Poultice

Exercise1.7.4

Rp.

Uveae ursi foil decocti 5.0 : 100.0

D.S. small spoonful 2-3 x per day

Exercise 1. 7.5

Rp.

Tiliae floris infusi 5.0 : 100.0

D.S. 2 spoonfuls 3 x per day

43

Exercise 1. 7.6

Rp.

Crataegi folii cum flore infusi 4.5 : 100.0

D.S. 2 spoonfuls 2-3 x per day

Exercise 1. 7.7

Rp.

Milefolii herbae infusi 5.0 : 100.0

D.S. 2 spoonfuls 2-3 x per day

The extraction of saponine compounds should be performed in a slightly alkaline medium,

which is reached by adding 0.1g of sodium carbonate or hydrogencarbonate or by adding 0.5g

of 10% ammonia solution to the 1.0g of drug. These substances are added to solvent, which is

dedicated to the pre-wetting of the drug.

Exercise 1.7.8

Rp.

Verbasci floris infusi 1.5 : 100.0

D.S. Drink during the day

Exercise 1.7.9

Rp.

Betulae folii infusi 5.0 : 100.0

D.S. Use 1 spoonful 3-4 x per day

Tinctures are usually alcoholic extracts from drugs or the ethanol solutions of dry extracts.

They are prepared by maceration at room temperature, the dissolution of the dry extracts, and

by percolation and stirring the extraction.

44


1. Maceration: The prescribed amount of drug is poured into a suitable vessel, along with the

prescribed amount of solvent. The vessel is closed and left to stand for 7 days and is stirred

occasionally. The obtained liquor is decanted and the drug is pressed out. Both liquors are

mixed and replenished with solvent which was used for washing the drug previously. Then

the liquor is left to stand in a dark, cool place for at least 12 hours to become transparent.

Then the transparent liquor is decanted, while the drug on the filter is washed with an

adequate amount of solvent so that the prescribed quantity of the tincture can be received.

2. Dissolution: The prescribed amount of the solvent is added to the prescribed amount of

dried extract. The vessel is closed and left to stand in a dark place and stirred occasionally

until it is dissolved. The liquid is then left to stand once more in a dark, cool place for at least

12 hours until it becomes transparent. Then the transparent liquor is decanted. The filter is

washed with an adequate amount of the solvent so that the prescribed quantity of the tincture

can be received.

3. Percolation: The drug is wetted with the prescribed quantity of solvent and left to stand for

about 6 hours. Then the drug is transferred to a percolator along with an appropriate quantity

of solvent so that the drug could be immersed. The percolator is closed and left to stand for 24

hours. The liquor flows out through the half-open cock and solvent is added continually. Flow

velocity is about 1/50 of percolator volume per hour. When 1/2 of the prescribed volume of

the tincture is obtained, the percolation is stopped. Then the rest of liquor contained in the

drug is left to drip out. The drug is then removed, pressed out and both liquors are mixed and

refilled to the prescribed weight.

Extracts are concentrated liquids, either dried or semi-solid, prepared by percolation or

maceration using alcohol or other suitable solvents.


The ratio of dried drugs to solvent and liquid extracts is usually 1 : 1.

Semi-solid and dried extracts are usually transformed to the desired consistency by the

evaporation of the solvent under reduced pressure and/or a reduced temperature, if

necessary.

45

Standardized extracts are adjusted to the defined content of the substance by using

suitable inert substances such as lactose or dextrin.

Selected pharmacopoeial tinctures: Arnicae tinctura, Aurantii amari pericarpi tinctura,

Beladonnae folii tincture, Cinnamomi tincture, Gallarum tincture, Gentianae tincture,

Ipecacuanhae tincture normata, Myrrhae tincture, Tinctura amara, Tormantiallae tincture,

Valerianae tinctura

Selected pharmacopoeial fluid extracts: Matricariae extractum fluidum, Plantaginis extractum

fluidum.

46

1.8 Eye drops

Eye drops are sterile, aqueous or oily solutions, emulsions or suspensions of one or more

active substances intended for insertion into the eye.

Ensuring the sterility of eye drops

Preparation in suitable environmental conditions (grade A, in the case that then

follows sterilization in an autoclave - grade C)

Using sterile or microbiologically safe drugs and other excipients (sterile water as

solvent).

Sterilization of the preparation (membrane filtration – pharmaceutical practice).

Suitable containers – glass or plastic eye-dropper bottle (sterile with integrated

dropper, secure, airtight).

Requirements and excipients

Clarity – eye drops examined under suitable conditions of visibility, are practically

clear and practically free from particles.

Tonicity – lacrimal fluid is isotonic to the blood. Eye drops are considered to be

isotonic when its tonicity is equal to 0.9% of the sodium chloride solution. Hypotonic

eye drops must be adjusted for isotonicity by the addition of sodium chloride, sodium

nitrate (for drugs based on Ag+ ions), glucose, mannitol and others. Hypertonic eye

drops are not adjusted.

pH – buffers (phosphate, borate, acetate) are used to minimize pH change during

shelf life because this could affect a drug’s solubility, stability and consequently, its

bioavailability.

Sterility – eye drops must be sterile. Sterility is achieved through membrane filtration

(pore size less than 0.22 µm) into a sterile container. Other methods include dry heat,

autoclaving (steam under pressure) or gas sterilization with ethylene oxide.

Ophthalmic solutions are generally packaged in multi-dose containers. Since there is

the possibility of inadvertent bacterial contamination of the contents with repeated

patient use, a preservative must be added. Preservatives should be safe in regard to

47

patient sensitivity and should be compatible with the other ingredients in the

formulation.

Preservatives (usually quaternary ammonium compounds or organic mercurials) that

are commonly used in ophthalmic preparations are listed in Table 1. Eye drops can not

contain a antimicrobial preservative, if the doctor requires so (sine antimicrobico!). In

this case the eye drops are intended for one use only. Eye drops intended for use in

surgical procedures do not contain antimicrobial preservatives; they are dispensed

from single-dose containers.

The particle size of ophthalmic suspensions must be kept to a minimum to prevent

irritation of the eye and must fall within the pharmacopoeia limit. It is recommended

that the particles should be less than 10µm in size to minimize eye irritation. The

micronized form of the drug can be used to meet this requirement.

Volume of eye drops should not be bigger than 10ml if it is not prescribed or

approved otherwise.

Labels: Red labels

Expiration date - usually 1 month; longer shelf life of preparations has to be approved

by the State Institute for Drug Control

Regime of application

Storage conditions

Only for external use

Date of preparation

Address of pharmacy

Pharmacist´s signature

Important abbreviations:

o O.d. - right eye

o O.s. - left eye

o O.e. - each eye

o O.b.- both eyes

48

o ODS - both eyes

Labeling for multi-dose preparations

o Interval after initial opening for use of eye drops - 4 weeks (during shelf life).

o Added antimicrobial preservative – cum antibicrobico (c.a.).

Labeling for single-dose preparations

o Contains amount of eye drops intended for total or partial use on 1 occasion

only!!!

o Preservatives are not permitted - sine antimicrobico (s.a.)

o For one application only after opening (immediately)

49

Table 1. Compatibility of preservatives with drugs

DRUG

Benzalko- Nium chloride 0.01%

Carbethopen-deciniumbro-mide 0.02%

Phenylmercuric borate (nitrate, acetate) 0.001-0.002%

Thiomersal 0.002 -0.01%

Chlorhexidin- diacetate 0,01%

Note

Acidum boricum Argenti nitras Argenti diacetyltannas albuminatus

Atropini sulfas monohydricus

Calcii chloridum Ethylmorphini hydrochloridum dihydricum

Epinephrini tartras

Fluoresceinum natricum

Suitable for single-dose preparation

Homatropini hydrobromidum

Kalii iodidum Natrii iodidum Natri tetraboras decahydricus

Physostigmini salicylas

Pilocarpini hydrochloridum

Procaini hydrochloridum

Resorcinolum Scopolamini hydrobromidum trihydricum

Tetracaini hydrochloridum

Zinci sulfas heptahydricus

Note: - suitable

- recommended

- unsuitable

- contradictory information

50

Table 2. Preservatives for eye preparations

GROUP

Range of used concentration (%)

Recommended concentration (%)

Range of pH for optimal activity

Note

Quarternary ammonium compounds

0.004 – 0.02

4 - 10 activity is higher at

neutral and basic pH

Benzalkonium chloride 0.01 – 0.02 usually in combination

with EDTA

Benzethonium chloride 0.01 – 0.02

Cetylpyridinium chloride 0.01

Cetrimide

0.01 – 0.1

Carbethopendecinium bromide 0.02

Polyquaternium-1 (polyquat) 0.02 -0.3 0.02 new,

limited usage

Organic mercurials 0.001- 0.04 6 - 8

Phenylmercuric borate

0.001 – 0.004

Phenylmercuric nitrate

0.002

Phenylmercuric acetate

0.001 – 0.004

Thiomersal

0.002 – 0.02

0.002 – 0.01

Aromatic and alifatic alkohols 0.5 – 0.9 4 - 6

Chlorbutanol 0.5

Benzyl alcohol 0.5

Fenylethyl alcohol 0.25 – 0.5

Esters of p-hydroxybenzoic acid (parabenes)

max. 0.1 4 - 8 Used rarely in

combination with other preservatives; low

efficiency, irritability

methylparabene 0.015 – 0.05

propylparabene 0.005 – 0.01

Others

chlorhexidine

0.01 – 0.05

0.01

6 - 8

51

EXAMPLES

Exercise 1.8.1

Acidi borici oculoguttae – Eye drops with boric acid – in pharmacopoeia;

Synonymum. Collyrium acidi borici

Acidum boricum 0.169 Thiomersalum 0.0002

Aqua purificata (sterilisata) ad ……..10.0

Preparation procedure: Dissolve 0.0002g of thiomersal (preservative, use 0.1% solution) in

9g sterile water warmed to 60-70 °C. Dissolve boric acid (API) in this solution. After cooling,

add evaporated water to 10.0 g. Sterilize by membrane filtration (0.22 µm) and fill into the

suitable container in environment of grade A. It is possible also to sterilize it in final

container by autoclaving (15 minutes, 121 ºC).

Phenylmercuric borate (0.01g/l) is another suitable preservative.

Storage conditions: Keep out of light!

Notes: It is usually dispensed from a 10ml container

If the doctor prescribed Solutio acidi borici or Acidum boricum solutum, and from the

prescription it is obvious that the preparation is intended for eye administration, Acidi borici

oculoguttae is dispensed.

Exercise 1.8.2

Chloramphenicoli oculoguttae – Eye drops with chloramphenicol – in pharmacopoeia

Synonymum. Collyrium chloramphenicoli

Chloramphenicolum (250) 0.05 Acidum boricum 0.15 Natrii tetraboras decahydricus 0.03 Thiomersalum 0.0002

Aqua purificata (sterilisata) ad 10.0

Preparation procedure: Dissolve sodium tetraborate, boric acid and thiomersal (preservative,

use 0.1% solution) by warming in approximately 9g of sterile water. When the temperature

descreases to approx. 70C, add powdered chloramphenicol (250µm), mix the solution at the

52

same temperature until all chloramphenicol is dissolved. After cooling, add evaporated water

to 10.0g. Sterilize by membrane filtration (0.22µm) and pour it into a suitable container in a

grade A environment.

Phenylmercuric borate (0.02g/l) is another suitable preservative.

Storage conditions: Keep away from light!

Notes: It is usually dispensed from a 10ml container. It cannot be dispensed without a

prescription.

Exercise 1.8.3

Fluoresceini natrici oculoguttae 2.5% – Eye drops with sodium fluorescein – in

Pharmacopoeia

Fluoresceinum natricum 0.25 Natrii chloridum 0.20 Thiomersalum 0.0002


Preparation procedure: First, dissolve thiomersal (preservative, use 0.1% solution) and

sodium salt of flourescein and sodium chloride. Add evaporated water to 10.0g. Sterilize by

membrane filtration (0.22µm) and pour into a suitable container in a grade A environment.



Exercise 1.8.4

Kalii iodidi oculoguttae – Eye drops with potassium iodide – in pharmacopoeia;

Synonymum. Collyrium kalii iodati

Kalii iodidum 0.20 Natrii chloridum 0.02 Natrii thiosulfas pentahydricus 0.002 Thiomersalum 0.0002


Preparation procedure: First, dissolve thiomersal (preservative, use 0.1% solution) in 9g of

sterile water, then sodium thiosulphate pentahydrate, potassium iodide and sodium chloride.

53

Add evaporated water to 10.0g. Sterilize by membrane filtration (0.22µm) and pour it into a

suitable container in a grade A environment.



Exercise 1.8.5

Natrii tetraboratis oculoguttae cum acido borico - Eye drops with sodium tetraborate

and boric acid – in pharmacopoeia;

Synonymum. Natrii teraboratis oculoguttae, collyrium boraxatum

Acidum boricum 0.175g Natrii tetraboras decahydricus 0.025g Thiomersalum 0.0002g

Aqua purificata (sterilisata) ad 10.0g

Preparation procedure: Dissolve 0.0002g of thiomersal (preservative, use 0.1% solution) in

9g of sterile water warmed to 60-70°C. Dissolve boric acid and sodium tetraborate

decahydrate into this solution. After cooling, add evaporated water to 10.0g. Sterilize by

membrane filtration (0.22µm) and pour into a suitable container in a grade A environment. It

is also possible to sterilize the eye drops in the final container by autoclave (20 minutes,

121ºC).



Exercise 1.8.6

Pilocarpini hydrochloridi oculoguttae – Eye drops with pilocarpine hydrochloride – in

pharmacopoeia; Synonymum. Pilocarpini oculoguttae, collyrium pilocarpinii chlorati

Pilocarpini hydrochloridum 0.1 0.2 Carbaethopendecinii bromidum 0.002 0.002 Acidum boricum 0.127 0.85 Natrii tetraboras decahydricus 0.003 0.002

Aqua purificata (sterilisata) ad….10.0 ad 10.0

Preparation procedure: Dissolve boric acid (API) and sodium tetraborate decahydrate (API)

in sterile water (carbon dioxide-free) warmed to 60-70°C. After cooling, add pilocarpine

54

hydrochloride and carbethopendecinium (preservative, use 0.5% solution) bromide. Add

evaporated water to 10.0g. Sterilize by membrane filtration (0.22µm) and pour into a suitable

container in a grade A environment.



Exercise 1.8.7

Zinci sulfatis oculoguttae – Eye drops with zinc sulphate - in pharmacopoeia;

Synonymum. Collyrium zinci sulfurici

Zinci sulfas heptahydricus 0.025 Acidum boricum 0.162 Natrii tetraboras decahydricus 0.003 Thiomersalum 0.0002


Preparation procedure: Dissolve 0.0002 g of thiomersal (preservative, use 0.1% solution) in

9g sterile water warmed to 60-70°C. Dissolve boric acid and sodium tetraborate decahydrate

into this solution. After cooling, dissolve zinc sulphate decahydrate. Add evaporated water to

10.0g. Sterilize by membrane filtration (0.22µm) and pour into suitable container in a grade

A environment. It is also possible to sterilize the eye drops in the final container by autoclave

(15 minutes, 121ºC).


Notes: It is usually dispensed in a 10ml container

Exercise 1.8.8

Rp.

Argenti nitratis oculoguttae 1% - 10.0 D.S. For application into the eyes of newborns after birth

Sine antimicrobico! Suo nomine. Pro ordinatione.

Note: Sine antimicrobico! – Without preservative!

Suo nomine. - Write name of preparation on the label. Pro ordinatione. – Intended for

medical office.

55

Exercise 1.8.9

Rp.

Sol. Atropini sulfatis 0.5% 10.0 D.S. Eye drops. 1 drop twice a day into conjuctival sac. Sub signo

veneni!

Notes: Sub signo veneni! – Mark as poison!

Exercise 1.8.10

Rp.

Tetracaini chloride 0.025 Aq. sterilisatae ad 10.0 M.f. collyr.

D.S. Cum formula, pro ordinatione. Sine antimicrobico!

Notes: Cum formula – Write the composition on the label

Exercise 1.8.11

Rp.

Ethylmorphini hydrochloride 0.05 Aq. sterilisatae ad 10.0 M.f. collyr.

D.S. Eye drops. 1 drop twice a day into conjuctival sac.

Exercise 1.8.11

Rp.

Physostigmini salicylatis 0.01 Aq. sterilisatae ad 10.0 M.f. collyr.

D.S. Eye drops. 1 drop four times a day into conjuctival sac.

56

Exercise 1.8.12

Rp.

Homatropini hydrobromidi 0.1 Aq. sterilisatae ad 10.0 M.f. collyr.

D.S. Eye drops. Suo nomine. Pro ordinatione. Sub signo veneni!

Exercise 1.8.13

Rp.

Scopolamini hydrobromidi 0.01 Aq. sterilisatae ad 10.0 M.f. collyr. D.S. Eye drops. 1 drop four times a day into conjuctival sac.

Sub signo veneni!

57

1.9 Eye lotions

Eye lotions are sterile, aqueous solutions intended for rinsing or bathing the eye, or for

impregnating eye dressings. The maximum volume of multi-dose eye lotions is 200 ml.

Excipients

Sterile water.

Excipients for adjustment of osmotic pressure.

Viscosity increasing agents.

Excipients for the adjustment and stabilization of pH.

Preservatives.

Eye lotions without preservatives that are prescribed by a doctor, are dispensed in single-dose

containers. Eye lotions intended for open wounds, or for surgery, are not allowed to contain

preservatives and are put into single-dose containers. Per visual examination, eye lotions

should be clear and without particles.

EXAMPLES Exercise 1.9.1

Acidi borici aqua ophtalmica – Eye lotion with boric acid

Acidum boricum 1.690 g Thiomersalum 0.002 g

Aqua purificata ad 100.0 g

Preparation procedure: Dissolve 0.0002g of thiomersal (preservative) in 90g sterile water

warmed to 60-70°C. Dissolve boric into this solution. After cooling, add evaporated water to

100.0g. Sterilize by membrane filtration (0.22µm) and pour into a suitable container in a

grade A environment. It is possible also to sterilize it in final container by autoclaving (15

minutes, 121ºC).


Notes: It is usually dispensed from a 100 ml container, maximum 200 ml. Separated

applicator must pass a sterility test.

58

1.10 Nasal drops

Nasal drops are solutions, emulsions or suspensions intended for the instillation, or spraying,

into the nasal cavities. Although nasal application is considered to be an alternative pathway

for systemic administration, most nasal drugs prepared in the pharmacy are used for their

local effect.

Nasal mucosa is partially covered with cilia epithelium and mucus, which trap and remove

dust and pathogens from the air as it flows through the nasal cavity. Therefore the

composition of nasal preparation should not adversely affect the function of the nasal mucosa

and its cilia. For this reason, hydrophilic preparations are prefered, and lipophilic diluents

such as liquid parafine and linseed oil are not permitted. Parabenes (negative effects on the

cilia) and borate buffers (toxic effects) are not suitable for nasal application.

Nasal mucosa is sensitive to hypotonic solutions, therefore aqueous nasal drops should be

isotonic (non-aqueous and lipophilic nasal drops are not adjusted). Rules for tonicity

adjustment are the same as they are in the case of eye drops.

Excipients

Viscosity-increasing agents (cellulose derivates – HEC, HPMC, MC; others - PVA, PVP)

are added to formulations to increase bioavailability by ensuring that there is longer contact

time. Nasal drops very often contain excipients for smell correction (essential oils).

Preservatives (usually quaternary ammonium compounds or organic mercurials) are added to

ensure the microbial quality of aqueous nasal drops. Carbethopendecinium bromide is

preferred because of its eutrofic effect on the nasal mucosa.

Labels: red label - information for patients, storage conditions, name of added preservative,

sterility (for preparations intended for surgical procedures)

Shelf life: maximum 1 month

Amount: 10-30g

59

EXAMPLES Exercise 1.10.1

Acidi borici rhinoguttae cum ephedrino – Nasal drops with boric acid and ephedrine –

in pharmacopoeia; Synonymum. Acidi borici cum ephedrino naristillae

Ephedrini hydrochloridum 0.2 Acidum boricum 0.6


Preparation procedure: Dissolve boric acid in purified water warmed to 60-70°C. After

cooling, add ephedrine hydrochloride. Add evaporated water to 10.0g . Filter.

Storage conditions: Cold place (8-15°C); Keep away from light!

Notes: this cannot be dispensed without a prescription. It can be used for a maximum of 1

week.

Shelf life: 1 month

Exercise 1.10.2

Rp.

Argenti diacetyltannatis albuminati 0.1 Aq. purificatae Aq. menthae piperitae aa ad 10.0 M.f. sol.

D.S. Nasal drops. Half of dropper to each nostril three times a day

Preparation procedure: Place a colloidal silver on the surface of a mixture of purified water

and peppermint aromatic water. Let it slowly hydrate. Do not forget to add an excipient for

tonicity adjustment. Mix the prepared colloidal solution. Filter through gauze.


Shelf life: 3 weeks

60

Exercise 1.10.3

Rp.

Scopolamini hydrobromidi 0.02 Agari 0.04 Aq. purificatae ad 20.0 M.f. sol

D.S. Nasal drops Ad manus medici! Cum formula. Sub signo veneni!

Preparation procedure: Do not forget to add an excipient for tonicity adjustment, as well as a

suitable preservative (use in form of a solution)! Dissolve agar (viscosifier) into a small

amount of boiled purified water. Dissolve pilocarpine hydrochloride in the rest of the water

containing the preservative and excipient for tonicity adjustment. After cooling, mix the two

solutions together.


Shelf life: 1 month

Exercise 1.10.4

Rp.

Ephedrini hydrochloride 0.1 Carbethopendecinii bromidi 0.01 Foeniculi etherolei gtt I Sol. methylthionii chloridi 0,5% gtt II Methylcellulosi 0.2 Sol. natrii chloridi isoton ad 20.0 M.f. sol.

D.S. Nasal drops. Apply 3 times a day.

Preparation procedure: Layer methylcellulose on the surface of half amount of isotonic

solution of NaCl. Let it hydrate slowly (30 minutes). Dissolve ephedrine hydrochloride (API),

carbethopendecinium bromide (preservative) in the rest of isotonic solution of NaCl, and add

one drop of fennel oil and two drops of methylene blue. Mix the solutions together.


Notes: It can be used for a maximum of 1 week.

61

Shelf life: 1 month

Exercise 1.10.5

Rp.

Dexamethasoni 0.005 Mucilaginis methylcellulose 6.0 Aq. Purificatae ad 20.0 M.f. suspensio.

D.S. Nasal drops. 3 drops to each nostril 5 times a day

Preparation procedure: Use the previously prepared solution of dexamethasone in propylene

glycol and a 2.5% viscous solution of methylcellulose (PC 2009). Do not forget to add a

suitable preservative (use in form of a solution)!


Shelf life: 1 month

62

1.11 Ear drops

Ear drops are solutions, emulsions or suspensions suitable for application to the auditory

meatus without exerting harmful pressure on the eardrum. They may also be placed in the

auditory meatus by means of a tampon impregnated with the liquid. They are designed

especially for external ear treatment (for softening and dissolution of cerumen – ear wax,

cleaning of the external ear canal, dermatitis of the external ear canal, and infection). They are

rarely used for treatment of the innner ear.

Excipients

Unlike eye and nasal drops, ear drops are most often based on non-aqueous hydrophilic

diluents (ethanol, glycerol, propylen glycol, isopropyl alcohol, polyethylene glycols) or

lipophilic diluents (liquis paraffins, plant oils).

The outer auditory canal has a normal pH of 4 to 5, which has bacteriostatic or germicidal

effect to most microorganisms causing otitis. To adjust the pH to lower values, excipients

such as citric acid, boric acid, hydrochloric acid, sodium hydroxide, acetate, borate and

phosphate buffers are used. Preservatives and excipients for tonicity adjustment are only

added to aqueous ear drops. It is also possible to add viscosity-increasing agents.

Preparations for the application to the injured ear, particularly in such cases where the

eardrum is perforated, or prior to surgery, must be sterile, free from antimicrobial

preservatives and supplied in single-dose containers.

Package

Containers for ear drops are usually multi-dose, and made of glass or plastic with an

integrated dropper or screw cap with a dropper.

Ear drops should be heated to body temperature before application because cool ear drops can

lead to the irritation of the inner ear along with vertigo, nausea and vomiting.

Labels: red label - information for patients, storage conditions, names of any added

preservatives, and sterility (for preparations intended for surgical procedures)

Shelf life: maximum 1 month

Amount: 10-30 g

63

EXAMPLES

Exercise 1.11.1

Aluminii acetotartratis otoguttae – Ear drops with aluminum acetate tartare – in

pharmacopoeia; Synonymum. Instillatio aluminii acetico-tartarici

Aluminii acetotartratis solution 8.0 Aqua purificata 4.0

Ethanolum 60% 8.0

Preparation procedure: Mix solution of aluminium acetate tartrate with mixture of purified

water and ethanol 60 %.


Notes: The preparation may not be used if it contains any sediment

Shelf life: 1 month

Exercise 1.11.2

Rp.

Ac. borici 0.3 Ethacridini lactatis 0.01 Spiritus dilute ad 10.0 M.f. sol.

D.S. Ear drops. Insert a gauze pad and drop every 2 hours.

Preparation procedure: Dissolving


Notes: Flammable!

Shelf life: 1 month

64

Exercise 1.11.3

Rp.

Zinci sulfatis 0.1 Glyceroli 85% Aq. purificatae aa ad 20.0 M.f. sol.

D.S. Ear drops. A half dropper to the auditory meatus three times a day.



Shelf life: 1 month

Exercise 1.11.4

Rp.

Natrii carbonatis 0.4 Glyceroli 85% ad 20.0 M.f. sol. D.S. Ear drops. A half dropper to the auditory meatus three times a day.

and cover with wet gauze.

Preparation procedure: Dissolve sodium carbonate in glycerol in a close-neck bottle by

warming over the water bath.


Shelf life: 1 month

65

Exercise 1.11.5.

Rp.

Ac. salicylici 0.02 Ureae purae 1.0 Aq. Purificatae 8.0 Spiritus dilute ad 20.0 M.f. sol. D.S. Ear drops. A half dropper to the auditory meatus three to five times

a day.



Shelf life: 1 month

66

1.12 Emulsions

Emulsions are a two-phase system in which one liquid is dispersed throughout another liquid

in the form of small droplets. Polar liquid is called the water phase (water, aqueous solution)

and non-polar liquids are the oil phase (hydrocarbons, oils, higher alcohols, wax, etc.).Where

oil is the dispersed phase and an aqueous solution is the continuous phase, the system is

designated as an oil-in-water emulsion. Conversely, where water or an aqueous solution is the

dispersed phase and oil or oleaginous material is the continuous phase, the system is

designated as a water-in-oil emulsion.

Excipients

Emulsions are stabilized by emulsifying agents that prevent coalescence - the merging of

small droplets into larger droplets - and, ultimately, into a single separated phase. There are

three types of emulsifiers:

1. Surface-active agents – surfactants (reduce the surface tension at the

interface between oil and water molecules - adsorbant on the surface layer)

2. Macromolecular materials (primarily increase the viscosity of the external

phase (some are surface-active)

3. Finely divided solids (absorb on the interface and create a film of insoluble

particles around the dispersed droplets)

Emulsifying agents (surfactants) accomplish this by concentrating in the interface between the

droplet and the external phase, and by providing a physical barrier around the particle for

coalescence. Surfactants also reduce the interfacial tension between the phases, thus

increasing the ease of emulsification upon mixing.

Emulsions are intended for both internal and external use. Some emulsions intended for

topical application to the skin are known as liniments (Linimenta) and lotions (Lotiones).

Other preparations that have the characteristics of an emulsion should be designated

"emulsion" (e.g. ointments, suppositories).

General methods of solution preparation

Emulsions are prepared by a procedure suitable for the type and composition of the emulsion.

Generally, the temperature of both phases should be the same. The drug can be part of one or

67

both phases. O/w emulsions require antimicrobial agents because the aqueous phase is

favorable for the growth of micro-organisms. Preservatives that are commonly used in

emulsions include methyl-, ethyl-, propyl-, and butyl-parabens, benzoic acid, and quaternary

ammonium compounds. Antioxidants are required if the oil phase is an external phase of the

emulsion.

Preparation of the emulsion is comprised of several steps:

1. Preparation of the aqueous phase

2. Preparation of the oil phase

3. Emulsification

4. Homogenizing

Before preparing the emulsion, it is important to determine what type of emulsion is being

produced. The ratio of oil and aqueous phases and the type of emulsifier, are very important.

Ad 1. Preparation of the aqueous phase - all water soluble substances are dissolved in

water. In the case that the external phase is the aqueous phase, it is possible to add a substance

to the final emulsion. It is not recommended to add strong electrolytes to the final emulsion,

as the high concentration can break the emulsion.

Ad 2. Preparation of the oil phase - all hydrophobic substances are mixed together

(e.g. oils, fats, waxes, fatty acids, fatty alcohols) as well as substances soluble in the

hydrophobic phase.

Ad. 3 Emulsification is process where one phase is divided into small particles that are

dispersed simultaneously within the second phase. It is important that the temperature of the

phases should range from between 50 and 80C, depending on the nature of the product.

Emulsification can be carried out with mortar and pestle, shaking in the bottle, or using a

mixer or other mixing equipment.

Ad 4 Homogenization is a process using homogenizers where droplets of different

particle size in the primary emulsion are reduced to the desired size to ensure appropriate

stability of the preparation. For small volumes of products, this step can be skipped, or it can

be used a mixer.

68

Preparation according to incorporation of emulsifier we know several types of emulsification techniques

1. English technique – wet gum method

This is suitable for the preparation of w/o and o/w emulsions. The emulsifier is incorporated

into the phase in which it is more soluble (EXTERNAL), in part or in whole.

o/w emulsions

If the proportion of oil and water and emulsifier are similar, the gum is dissolved

in the water part to form mucilage, then rest of the water is added, and finally oil is

slowly added in portions while being agitated.

If there is a smaller amount of the oil phase, the water phase is divided into two

parts. In the first part, the emulsifier is dissolved, and then the oil phase is slowly

added, so a concentrated emulsion is created. Finally, the concentrated emulsion is

diluted with the remaining water.

w/o emulsions

The emulsifier is dissolved in the external oil phase, and then the water phase is

gradually added while being agitated.

Liquid emulsions can be prepared by shaking them in the bottle. The size of the bottle should

correspond with the volume of the preparation and must be dry, or rinsed by the outer phase.

Rinsing the interior walls of the bottles with the inner phase can result in the creation of an

opposite type of emulsion.

2. Continental technique – dry gum method

Suitable for the preparation of o/w emulsions, it is used to prepare the emulsion from a

polymer or “gum” type emulsifier (gum arabic, tragacanth, gelatin or other emulsifiers from

the group of macromolecular solid substances). The emulsifier is incorporated into the phase

in which it is practically insoluble (INTERNAL). The emulsifier is dispersed in the oil and

part of the external aqueous phase is added to the resulting suspension (for each emulsifier is

an individual volume of aqueous phase to prevent formation of clusters) and is stirred

intensively. A viscous emulsion base is created (in this stage the emulsifier slowly dissolves

69

in the added water). Oil is then added by parts and finally the rest of water is slowly added

while stirring rapidly until the emulsion is completed (o/w).

The continental technique is used for the incorporation of emulsifiers, where, during the first

stage of preparation, the emulsion w/o is created, and then, after adding the rest of the

aqueous phase, it is changed into an emulsion o/w. This phase inversion allows for the

preparation of a stable emulsion with lower mechanical energy.

3. “In situ” soap method

This method is suitable for the preparation of emulsions w/o and o/w. The emulsifier is a

soap, which is formed as a result of the reaction between the components of the oil phase

(higher fatty acids, which are part of the oils and fats) with components of the aqueous phase -

alkali (emulsion o/w – sodium hydroxide, sodium, potassium, ammonium carbonate,

trolamin; emulsion w/o – calcium, magnesium, aluminium hydroxide). Some reactions can be

accelerated with heat.

4. Method using a complex emulsifier

This method is suitable for the preparation of emulsions o/w. Substances forming a complex

emulsifier can be prescribed separately or in a mixture. If emulsifiers are separate, the English

(wet gum) technique is used. Each emulsifier is incorporated into the phase in which it is

more soluble, i.e. a primary emulsifier into the aqueous phase and a secondary emulsifier into

the oil phase. If the emulsifiers are in the mixture, [e.g. Cetostearyl alcohol emulsificans (type

A) and (B)] the continental technique is used. The mixture of emulsifiers is incorporated into

the oil phase.

70

EXAMPLES

English technique – wet gum method

- Procedure is the same as in the case of mucilage or gel preparation

Exercise 1. 12.1

Rp.

Methylcellulosi 1.5 Glyceroli 85% 5.0 Paraffini liquidi 30.0 Foeniculi etherolei 0.5 Aq. purificatae ad 100.0 M. f. emulsio

D.S. one spoonful 2 times a day

Preparation procedure: Use 2.5% mucilage of methylcellulose (calculate the amount of

methylcellulose mucilage). Add water to mucilage and homogenize. Finally, emulsify liquid

paraffin and foeniculi etheroleum.

Additional labels on package: Shake before use!

Shelf life: 14 days in the refrigerator

Exercise 1.12.2

Rp.

Tragacanthae 1.0 Polysorbati 80 0.6 Glyceroli 85% 10.0 Paraffini liquidi 25.0 Aq. purificatae ad 100.0 M. f. emulsio


Preparation procedure: Mix tragacanth with Polysorbate 80, glycerol and purified water.

Emulsify liquid paraffin into this mixture and homogenize.

71



Exercise 1.12.3

Rp.

Carmellosi natrici 1.0 Polysorbati 80 0.5 Paraffini liquidi 20.0 Aq. purificatae ad 100.0 M. f. emulsio


Preparation procedure: Use 2.0% mucilage of carmellose (calculate the amount of carmellose

mucilage). Add Polysorbate and water to mucilage and homogenize. Finally, emulsify liquid

paraffin.



Continental technique – dry gum method

Exercise 1.12.4

Rp.

Vanillini 0.01 Ethanoli 96% 5.0 Sirupi simplicis 20.0 Carmellosi natrici 1.0 Polysorbati 80 0.5 Paraffini liquidi 20.0 Aq. purificatae ad 100.0 M. f. emulsio

D. S. one spoonful 3 times a day

72

Preparation procedure: Mix solid carmellose with Polysorbate 80 and liquid paraffin. Add 12

g of purified water at once and mix rapidly and thoroughly as soon as you hear clicking

sound. Then add rest of purified water and sirupus simplex. Finally, admix vanilin in ethanol.



Exercise 1.12.5

Rp.

Methylcellulosi 0.5 Polysorbati 80 0.5 Helianthi olei 10.0 Sirupi simplicis 15.0 Aq. purificatae ad 100.0 M. f. emulsio

D. S. one spoonful 3 times a day

Preparation procedure: Mix solid methylcellulose with Polysorbate 80 and sunflower oil. Add

12 g of purified water at once and mix rapidly and thoroughly as soon as you hear clicking

sound. Then add rest of purified water and sirupus simplex.



“In situ” soap method

Exercise 1.12.6

Rp

Acidi oleinici 1.0 Ammoniae sol. 10% 25.0 Helianthi olei 74.0 M. f. emulsio

D. S. ammonium liniment

73

Exercise 1.12.7

Rp.

Calcii hydroxidi sol. 50.0 Lini oleum 50.0 M. f. emulsio

D. S. calcium liniment

Exercise 1.12.8

Rp.

Trolamini 2.5 Acidi oleici 5.0 Helianthi olei 20.0 Aq. purificatae ad 100.0 M. f. emulsio

D. S. cleaning emulsion

Exercise 1. 12.9

Rp.

Spiriti saponis kalini 0.5 Ammoniae sol. 10% 21.5 Camphorae 5.0 Ricini olei 13.0 Rapae olei 60.0 M. f. emulsio

D. S. camphor liniment

Preparation procedure: Note for exercises 1. 10.6, 1.10.7, 1. 10.8 and 1. 10.9: Put all

ingredients into a dry bottle and shake. For shaking, use a 100 ml-volume bottle if you

prepare a 50 ml-volume emulsion!


Shelf life: 1 month in the refrigerator

74

Method using a complex emulsifier

Exercise 1.12.10

Rp.

Propylenglycoli 2.5 Neoaquasorbi 5.0 Helianthi olei 5.0 Paraffini liquidi 3.0 Polysorbati 80 1.0 Aq. conservantis ad 100.0 M. f. emulsio

D. S. for external use

Exercise 1.12.11

Rp.

Aurantii etherolei 0.5 Cholesteroli 1.0 Adipis lanae 2.5 Trolamini 3.5 Stearini 5.0 Cerae albae 7.5 Helianthi olei 12.5 Aq. purificatae 90.0 M. f. emulsio


Exercise 1.12.12

Rp.

Paraffini liquidi 49.0 Alcoholi cetylici 1.0 Natrii laurylsulfatis 1.0 Aq. purificatae ad ….. 100.0 M. f. emulsio


75

Preparation procedure: Note for exercises 1. 10.10, 1. 10.11 a 1. 10.12: A mixture containing

all the substances is heated in a beaker over a water bath (70ºC) until they are entirely melted.

The emulsion is prepared (homogenized) by hand, and mixed three times in one-minute

intervals with 30-second breaks. Volatile substances (essential oils) are then added to the final

emulsion.


Shelf life: 1 month in the refrigerator

76

1.13 Suspensions

Suspensions are (at least) two-phase systems consisting of a finely divided solid (inner phase)

dispersed into a liquid vehicle (outer phase).

In these preparations, the substance distributed is referred to as the dispersed phase and the

vehicle is known as the dispersing phase or dispersion medium. Together, they form a

dispersed system (the term refers to a system in which one substance (dispersed phase) is

distributed as discrete particles, throughout a second substance (continuous phase or vehicle)).

Suspensions are liquid dosage forms intended for oral, topical and parenteral application. In

many dosage forms can be the active ingredient(s) suspended in a suitable vehicle (ointments,

creams, suppositories, etc.). The absorption of the drug from the suspension (after p.o.

application) is faster than that from solid dosage forms, but slower than those absorbed from

solutions.

Solid particles in the form of a pharmaceutical suspension should be homogeneously

dispersible after shaking, they should have the desired, constant particle size and

sedimentation after shaking should start only after the time needed to administer the dosage (≈

2 min).

Suspensions are usually coarse dispersed systems, which come through physical changes

depending on time. The stability of the preparation is affected by solid particle size, surface

wettability of solids by liquid vehicle and viscosity of the outer phase.

Basic properties of suspensions

Liquid, easy application

Accurate dosing and expected therapeutic effect

Slow sedimentation (= settle)

Easy sediment re-shaking (re-suspendation)

Duration and onset of action can be controlled

Constant particle size

Pleasant appearance

77

Resistant to microbial contamination

Excipients

Liquid media – water, ethanol, glycerol, propylene glycol, plant oils, liquid paraffin

Viscosity-increasing agents (thickeners) – water dispersion of colloidal silicon

dioxide, bentonite magma, mucilages of macromolecular materials (cellulose

derivatives, gums)

Substances to improve surface wettability – surfactants, ethanol, glycerol,

propylene, glycol

Substances to improve flocculation – electrolytes, surfactants, polymers

Substances to adjust pH value – buffers, citric acid

Antimicrobial preservatives – paraaminobenzoic acid derivatives (parabens),

carbethopendecinium bromide, ethanol

Antioxidants – propyl gallate, tocoferol acetate

Taste and smell-improving agents – syrups, sweeteners, aromatic waters

Colours

Classification of suspensions according to:

Method of Application

1. Oral suspensions (Mixturae)

2. Topical suspensions - Suspension lotions (Lotiones suspensae)

- Liquid powders (Pulveres adspersorii liquidi)

78

Surface wettability and quality of solvating surface

Non-flocculated Flocculated Floated

Wettability perfect good bad

Pharmaceutical applicability + + -

Supernatant cloudy bright

Sediment

small large

increasing in time decreasing in time

Sediment re-shaking not easy „caking“ not problematic impossible

General methods of suspension preparation

1. Dispersion of solid substance in liquid medium

a) Solid phase preparation

Crushing, grinding or milling of solid materials to the required particle size

(topical preparations 10 – 100µm, oral suspensions < 200µm).

Sieving, homogenization.

b) Liquid phase preparation

Dissolving of soluble active substances and excipients in a liquid medium.

c) Dispersion

Liquid phase is slowly added (in parts !!!) to powders by continual mixing in

mortar and pestle (initially a prepared concentrated suspension is used, which

is subsequently diluted).

Semi-solids immiscible with water (tars, etc.) should be first dissolved in a technical

auxiliary substance (ether, acetone), then a mixture of powders should be added. This

blend should be mixed until completely evaporated (working in fume hood) of organic

solvent (absorption of semisolid material on the surface of solid particles).

79

Volatile solid substances (menthol, camphor) should be added to solid particles after

dissolving in small amount of solvent (ethanol).

Liquid ingredients immiscible with water (oils, paraffins) should be emulsified into

the completed suspension.

Drugs soluble in the outer phase should be added in step (b) or at the end of the

preparation procedure.

2. Condensation

The group of methods based on the principle of the crystallization of the substance from its

molecular or ionic dispersion by:

a) Temperature change

b) Solvent change

c) pH value change

d) Chemical reaction (active substance is different from entry materials!)

Packaging

Packaging is specific for each type of preparation and administration method (usually narrow

or wide-neck bottles). There must be an extra space of packaging reserved for the shaking of

the suspension before use.

Labels

Basic labels

o Colour (white – oral, injection; red – topical; yellow – laboratory reagents)

o Label requirements (information for the patient, dosage, date, address of

pharmacy, signature, expiration, quantity)

Additional labels - important notices

o Shake before use! Corrosive! Flammable! For animals only! Poison!

o Storing conditions (Keep out of light!; Keep cold!)

Shelf life

Shelf life is specified by the pharmacist with respect to:

80

o National authorities´ recommendations

o Scientific literature

o Physico-chemical and microbiological stability

o Duration of therapy

For most prepared pharmaceutical suspensions, there is a maximum shelf life of 1 month if

they are antimicrobially protected (preservatives) or are prepared from non-aqueous solvents.

Shelf life is only 1 week for water antimicrobially non-protected preparations (2 weeks,

when stored in cold conditions).

Note: Use stainless steel mortar and ceramic pestle when using coloured substances (coal tar,

bismuth tribromphenolate, etc.)

EXAMPLES

Exercise 1.13.1

Zinci oxidi suspensio – Suspension of zinc oxide

Zinci oxidum (45) 25.0 Talcum (45) 25.0 Glycerolum 85% 25.0 Bentoniti magma 25.0

M. f. suspension

Preparation procedure: Admix the blend of ZnO and talc in glycerol. Slowly add bentonite

magma.


Storage conditions: Store in wide-neck bottle.

Exercise 1.13.2

Sulfuris suspensio – Sulphur suspension

Sulfur ad usum externum 2.5 Ether solvens 12.5 Ethanolum 60% 12.5

M. f. suspension

81

Preparation procedure: Add mixture of alcohol and ether to sulphur. Work in close-neck

bottle.

Additional labels on package: Shake before use! Inflammable!

Storage conditions: Cold place (8-15°C).

Shelf life: 1 month

Dispensing: Apply a piece of cotton-wool to the mouth of the bottle when shaking and apply

on the desire area.

Exercise 1.13.3

Rp.

Magnesii oxidi 10.0 Acaciae mucilaginis 5.0 Aq. purificatae ad 100.0

M. f. suspension

D. S. 3 x 1 spoonful

Preparation procedure: Prepare acaciae mucilage according to pharmacopoiea. (33% GA in

Aqua conservans). Suspend magnesium oxide in this mucilage and dilute the concentrated

suspension with the rest of the water.

Adjustment: narrow-neck bottle

Additional labels on package: Shake before use!, c.p.

Storage conditions: cold place (8-15°C)

Shelf life: 1-2 weeks

Exercise 1.13.4

Rp.

Calcii carbonatis 1.0 Bismuthi subnitratis 1.0 Methylcellulosi mucilago 20.0 Aq. purificatae ad 100.0 M. f. suspensio

D. S. 3 x 1 spoonful

82

Preparation procedure: Use 2.5% methylcellulose mucilage. Disperse the powder mixture in

this mucilage and add of the remaining water.

Adjustment: narrow-neck bottle


Storage conditions: cold place (8-15°C)


Exercise 1.13.5

Rp.

Calcii chloridi 4.0 Natrii hydrogenocarbonatis 6.25 Aq. purificatae ad 50.0 M. f. suspensio

D. S. Use between meals

Preparation procedure: Mix two solutions – a prepared 50% solution of calcium chloride and

solution of sodium hydrogencarbonate in water. Add the remaining water. The active

substance is formed by chemical reaction



83

Exercise 1.13.6

Rp.

Bismuthi tribromphenolatis 1.0 Balsami peruviani 4.0 Ricini olei 15.0 M. f. suspensio

D. S. Visnevski balm

Preparation procedure: Admix the solid substance in a small amount of castor oil, then add

the rest of the oil and balsam of Peru. Work in a stainless steel mortar.

Adjustment: wide-neck bottle


Shelf life: 3 months

Exercise 1.13.7

Rp.

Picis lithantracis 1.5 Zinci oxidi 20.0 Talci 20.0 Glyceroli 85% 15.0 Aerosoli dispersii ad 100.0

M. f. suspensio

Preparation procedure: Dissolve coal-tar in 7.5g of ether in one dish. Mix the powders in

another dish. Then add this mixture to the dissolved tar and mix it in a fume hood until all of

the ether has evaporated. Then add glycerine and the dispersion of silica dioxide. Work in a

stainless steel mortar.

Adjustment: wide-neck bottle


Shelf life: 1 month

84

Exercise 1.13.8

Rp.

Ichthamoli 0.5 Zinci oxidi 10.0 Talci 10.0 Calcii carbonatis 10.0 Glyceroli 85% 15.0 Aerosoli dispersii ad 100.0

M. f. suspensio

Preparation procedure: Prepare a powder mixture of zinc oxide, talc and calcium carbonate.

Add glycerine and the silica dioxide dispersion and then ichtammolum (hydrophilic liquid).

Adjustment: Wide-neck bottle


Shelf life: 1 month

Exercise 1.13.9

Rp.

Mentholi 1.0 Zinci oxidi 20.0 Talci 20.0 Glyceroli 85% 15.0 Ethanoli 96% 20.0 Aerosoli dispersii ad 100.0

M. f. suspensio

Preparation procedure: Dissolve menthol in ethanol, add the powder mixture, then the

glycerol and dispersion of silica dioxide.



Shelf life: 1 month

85

Exercise 1.13.10

Rp.

Tannini 2.0 Boli albi Talci aa 10.0 Helianthi olei 2.5 Aerosoli dispersii ad 100.0

M. f. suspensio

Preparation procedure: Mix a powder mixture of tanninum, white clay and talc with a

dispersion of silica dioxide and then emulsify sunflower oil (three-phase system).

Note: Add 0.5g of Polysorbate before adding Sunflower oil.



Shelf life: 1 month

86

2. Semi-solid preparations

Semi-solid preparations for cutaneous applications are intended for local or transdermal

delivery of active substances, and for their emollient or protective action. They are also of

homogeneous appearance. The preparations usually consist of either a simple or compound

base in which one or more active substances are dissolved or dispersed. According to its

composition, the base may influence the activity of the preparation.

The base may consist of natural or synthetic substances and may be single phase or multi-

phase. According to the nature of the base, the preparation may have either hydrophilic or

hydrophobic properties; it may contain suitable excipients such as antimicrobial preservatives,

antioxidants, stabilisers, emulsifiers, thickeners and penetration enhancers.

Semi-solid preparations for cutaneous applications intended for use on severely injured skin

must be sterile.

Categories of semi-solid preparations for cutaneous applications

Ointments

Creams

Gels

Pastes

Poultices (cataplasma)

Medicated plasters

According to their structure, ointments, creams and gels generally show a viscoelastic

behaviour and are non-Newtonian in character, e.g. plastic, pseudoplastic or thixotropic types

flow at high shear rates. Pastes frequently exhibit dilatancy.

Characteristics of individual semisolids

Ointments (unguenta)

87

Definition

An ointment consists of a single-phase base in which solids or liquids may be dispersed.

o Hydrophobic ointments

Hydrophobic ointments can absorb only small amounts of water. Typical bases used for their

formulation are hard, liquid and light liquid paraffins, vegetable oils, animal fats, synthetic

glycerides, waxes and liquid polyalkylsiloxanes.

o Water-emulsifying ointments

Water-emulsifying ointments can absorb larger amounts of water and can thereby produce

water-in-oil or oil-in-water emulsions after homogenisation, depending upon the nature of the

emulsifiers. Water-in-oil emulsifying agents such as wool alcohols, sorbitan esters,

monoglycerides and fatty alcohols, oil-in-water emulsifying agents such as sulfated fatty

alcohols, polysorbates, macrogol cetostearyl ether or esters of fatty acids with macrogols may

be used for this purpose. Their bases are the same as those of hydrophobic ointments.

o Hydrophilic ointments

Hydrophilic ointments are preparations that have bases that are miscible with water. The

bases usually consist of mixtures of liquid and solid macrogols (polyethylene glycols), and

may contain an appropriate amount of water.

Creams (cremores)

Definition

Creams are multi-phase preparations that consist of a lipophilic phase and an aqueous phase.

o Lipophilic creams

Lipophilic creams have as their continuous phase, the lipophilic phase. They usually contain

water-in-oil emulsifying agents such as wool alcohols, sorbitan esters and monoglycerides.

o Hydrophilic creams

Hydrophilic creams have as their continuous phase, the aqueous phase. They contain oil-in-

water emulsifying agents such as sodium or trolamine soaps, sulfated fatty alcohols,

88

polysorbates and polyoxyl fatty acid and fatty alcohol esters combined, if necessary, with

water-in-oil emulsifying agents.

Gels (gelata)

Definition

Gels consist of liquids gelled by suitable gelling agents.

o Lipophilic gels

Lipophilic gels (oleogels) are preparations whose bases usually consist of liquid paraffin with

polyethylene or fatty oils, gelled with colloidal silica, aluminium or zinc soaps.

o Hydrophilic gels

Hydrophilic gels (hydrogels) are preparations whose bases usually consist of water, glycerol

or propylene glycol gelled with suitable gelling agents such as poloxamers, starch, cellulose

derivatives, carbomers or magnesium-aluminium silicates.

Pastes (Pastae)

Definition

Pastes are semi-solid preparations for cutaneous applications containing large proportions of

solids finely dispersed in the base.

Poultices (Cataplasma)

Definition

Poultices consist of a hydrophilic heat-retentive base in which solid or liquid active

substances are dispersed. They are usually spread thickly on a suitable dressing and heated

before applying to the skin.

89

Medicated plasters (Emplastra medicata)

Definition

Medicated plasters are flexible preparations containing one or more active substances. They

are intended to be applied to the skin. They are designed to keep the active substance(s) in

close contact with the skin so that they may be absorbed slowly, or act as a protective or

keratolytic agent.

Semi-solid eye preparations (Ocularia semisolida)

Definition

Semi-solid eye preparations are sterile ophthalmic ointments, creams or gels designed for

application to the conjunctiva, and contain one or more active substances dissolved or

dispersed in a suitable base which does not irritate the conjunctiva. They have a homogeneous

appearance.

Semi-solid eye preparations are packed in small, sterilised collapsible tubes fitted or provided

with a sterilised cannula. The containers contain at most 10 g of the preparation, unless

otherwise justified and authorised. The tubes must be closed tightly to prevent microbial

contamination. The containers, or the nozzles of tubes, are of such a shape as to facilitate

administration without contamination.

Semi-solid nasal preparations (Nasalia semisolida)

Definition

Semi-solid nasal preparations (ointments, creams, gels, and pastes) are intended for

application into the nasal cavity, and consist of simple or compound bases, in which one or

more drugs are usually dissolved or dispersed. Hydrophilic semi-solid preparations are more

suitable for nasal application because of the favorable effect on the ciliated epithelium of the

mucosa. Therefore, it it preferred that:

- Hydrophilic ointment consisting of polyethylene glycols with different molecular

weight hydrophobic ointments, especially those that have hydrocarbon bases, should

be used only in rare cases,

90

- Hydrophilic creams, which are emulsion preparations o/w,

- Hydrogels, which are dispersions of polymer substances (e.g., cellulose derivatives,

polyacrylic acid derivatives, etc.) in water, or other hydrophilic solvent.

Semi-solid ear preparations (Auricularia semisolida)

Definition

Semi-solid ear preparations are ointments, creams, gels or pastes intended for application to

the external ear, auditory meatus, or tampons impregnated with the preparation. They are

supplied in containers fitted with a suitable applicator. Depending on the nature of the base

(constitutive excipient) they may have hydrophilic or lipophilic properties, and may also

contain other ingredients (such as antimicrobial agents, antioxidants, emulsifiers, etc.).

Semi-solid rectal preparations (Rectalia semisolida)

Definition

Semi-solid rectal preparations are ointments, creams or gels. They are often single-dose

preparations in containers with a suitable applicator.

Semi-solid vaginal preparations (Vaginalia semisolida)

Definition

Semi-solid vaginal preparations are ointments, creams or gels. They are also single-dose

preparations in containers with a suitable applicator.

Semi-solid oral preparations (Oromucosalia semisolida)

Definition

Semi-solid oral preparations are hydrophilic gels or pastes intended for use in the oral cavity

or in specific parts of the oral cavity, such as gingiva (gel on the gingiva, gingiva paste).

They may also be in the form of single-dose products.

91

Basic requirements for the preparation (manufacture) of semi-solid dosage

forms


Appropriate ways to ensure the microbial quality of semi-solid preparations for cutaneous

application are used during the preparation (manufacturing), packaging, storing and

dispensing (distribution); recommendations for this are provided in Microbiological quality of

pharmaceutical preparations (Ph. Eur).

Sterile drugs (Category 1 of microbiological quality of medicinal products) are produced

using materials and methods designed to ensure sterility and to avoid the introduction of

contaminants and the growth of micro-organisms; recommendations for this are provided in

Methods of preparation of sterile products (Ph. Eur).

Conditions for other (non-sterile) preparations must ensure that the quality of the drugs

fulfill the criteria for Category 2 (preparations for local use and for use in the respiratory tract)

or Category 3 (products for oral and rectal use) of the microbiological quality of drug

preparations.

Preparation (manufacture) of semi-solid dosage forms must be carried out

according to the guidelines (see below for general steps of preparation of

semi-solid dosage forms).

Preparation of semisolid drugs in the pharmacy follows the principles of

good manufacture practice (Public notice no. 255/2003) (See liquid

preparations).

Quality evaluation

In the manufacture of semi-solid preparations for cutaneous application, suitable measures

should be taken to ensure that the defined rheological properties will be fulfilled. Where

appropriate, the following non-mandatory tests should be carried out: measurement of

consistency by penetrometer, viscosity (apparent viscosity) and a suitable test to demonstrate

the appropriate release of the active substance(s).

Final semi-solid preparations are tested according to Czech Pharmacopoeia 2009:

92

Test for extractable mass or volume – performed in the semi-solid preparations

in single-dose containers,

Sterility – performed in ophthalmic preparations and preparations labeled as

sterile,

Particle size – performed in semi-solid suspension ophthalmic preparations,

Uniformity of content – performed in single-dose eye and ear preparations

containing drugs in the content less than 2 mg or less than 2% of the total weight,

Content evaluation – peformed for individual products.

Uniformity of weight – performed in single-dose eye and ear preparations,

Identification tests – performed for individual preparations,

Purity test – performed for individual preparations,

Labels

In addition to information required for all preparations, the label shall state:

- Where appropriate, that the product is sterile (i.e. in the case of dosage forms that may

not be sterile basically)

- For single-dose eye preparations – that the content is intended only for one usage,

- In multi-dose eye and ear preparations - that after first opening the product, it must be

used during a four-week period, (after which the content may not be used) if it is not

approved or determined otherwise.

Packaging

All semi-solid preparations should be stored in well-sealed containers. If the product contains

water or other volatile substances, it must be stored in airtight containers. When the product is

sterile, it must be stored in secure, sterile, airtight containers.

In the pharmacy, preparations are usually packed in plastic cups or wide-necked bottles with

screw caps. Semi-solid eye preparations are packed into small, sterilized, squeezable tubes

(metal or plastic) with a capacity of not more than 5g. The tubes must be closed and have an

applicator that ensures an uncontaminated application.

93

Because of the nature of active excipients, they may require protection from light and/or

storage at lower temperatures (cold or refrigerated). These preparations are prepared in the

pharmacy for time of need (individual production) or stocks (collective production). The

shelf-life of some of these products is determined by the State Institute for Drug Control

(SÚKL) recommendations (see the current table in the laboratory). For other preparations, the

pharmacist determines the shelf-life according to the nature and length of treatment for up to 1

month.

94

2.1 Ointments

One-phase hydrophobic ointments without drugs – ointment bases

One-phase hydrophobic ointments are usually prepared by the melting of all components

(including emulsifiers), preferably in an enamel mortar over a water bath, or under infrared

lamps. The mixture of all of the substances is melted all at once or by melting the substances

at the highest melting point and then adding more substances. If necessary, the melted mixture

is filtered through several layers of gauze to get rid of the impurities, and stirred while

continually scraping the mixture from the walls of the mortar. If the base contains a waxy

substance nature (beeswax, hard paraffin wax, stearin, etc.) do not accelerate the cooling

process by putting it in water or ice. This will change the consistency of the final product,

making it more stiff and non-homogenous than desired.

Pharmacopoeal ointments: Alcoholis cetylici unguentum, Alcoholum adipis lanae

unguentum, Unguentum constituens pro antibioticis, Unguentum emulsificans anionicum,

Unguentum emulsificans nonionicum, Unguentum, Unguentum ophtalmicum simplex,

Unguentum simplex.

EXAMPLES

Pharmacopoeal formulas

Exercise 2.1.1

Alcoholis cetylici unguentum

Alcohol cetylicus 2.0 Adeps lanae 15.0

Vaselinum album 83.0

Preparation procedure: Cetyl alcohol, wool fat and white Vaseline are melted; then the

mixture is stirred until cool.

Storage: Protect from light

95

Exercise 2.1.2

Alcoholum adipis lanae unguentum

Alcoholes adipis lanae 10.0

Vaselinum flavum 90.0

Preparation procedure: Alcoholes adipis lanae and yellow Vaseline are melted; then the

mixture is stirred until cool.

Storage: Protect from light.

Exercise 2.1.3

Unguentum constituens pro antibioticis

Adeps lanae 10.0 Paraffinum liquidum 10.0


Preparation procedure: Adeps lanae, liquid paraffin, yellow Vaseline are melted and then

mixed. The mixture is then filtered through a gauze and sterilized in a stream of hot air for 90

minutes at 140C.

Storage: Protected from light and store at a temperature from 8 - 15C.

Dispenzing: After opening, the ointment base must be used within 48 hours. It is used only for

the preparation of ointments with bacitracin, erythromycin, oxytetracycline, tetracycline,

chloramphenicol or other antibiotics , provided they are checked for stability.

Exercise 2.1.4

Unguentum emulsificans nonionicum

Polysorbatum 60 10.0 Alkohol cetylstearylicus 30.0 Paraffinum liquidum 10.0


Preparation procedure: Polysorbate 60, cetostearyl alcohol, liquid paraffin and white Vaseline

are melted and stirred until they have cooled.


96

Exercise 2.1.5

Unguentum ophtalmicum simplex

Adeps lanae 10.0 Paraffinum liquidum 10.0


Preparation procedure: Adeps lanae, liquid paraffin and white Vaseline are melted and then

mixed. The mixture is then filtered through three layers of gauze, poured into containers

suitable for sterilization and then sterilized with dry heat for 2 hours at 160 C. The semi-

cooled, sterilized ointment is agitated in the clean room of grade A and poured into suitable

containers.


Exercise 2.1.6

Unguentum simplex

Propylis gallas 0.01 Ethanol 96% (V/V) 1.0 ml Adeps suilus 90.0 Alcohol cetylicus 5.0

Cera alba 5.0

Preparation procedure: Cetyl alcohol, white wax and lard are melted over a water bath at

70C, and then propyl gallate, dissolved in 96% ethanol, is added dropwise and stirred until

cool.

Storage: Protect from the light.

One‐phasesolutionhydrophobicointments


1. One-phase solution hydrophobic ointments are prepared by dissolving the drug

in the ointment base at room temperature – this method is used when the

prescribed drugs form an eutectic mixture (menthol, camphor, β naphthol, phenol,

etc.) or when adding hydrophobic or volatile substances (e.g., methyl salicylate,

essential oils) to the base.

97

2. By dissolving the drug in the ointment base at higher temperature – this method is

used when it is known that all the drugs that are dissolved in the melted base have

remained dissolved after cooling and during storage. The stability of the drug at higher

temperature is very important. E.g., when there are incorporate volatile substances

used, such as menthol or camphor, these must be dissolved in a warm base (max. of

40°C), and then stirred until they have cooled down.

3. By dissolving the drug in an auxiliary liquid/volatile solvent and then mixing with

the ointment base

Hydrophobic liquid (vegetable oil, liquid paraffin) is used as an excipient, which may be part

of the formula, or may replace some of the hydrophobic component.

A volatile organic solvent (ether) may also be used as an excipient, and evaporates after being

mixed with an ointment base.

EXAMPLES

Exercise 2.1.7

Rp.

Mentholi 2.0 Unguentum lanalcoli ad 50.0 M. f. ung.

D. S. apply ointment to the skin

Preparation procedure: Menthol is comminuted. Unguentum lanalcoli is melted over water

bath at 40 ºC and then added to comminuted menthol. Finally, mixture is stirred until cool.

Exercise 2.1.8

Rp.

Camphorae 1.5 Vaselini albi ad 50.0 M. f. ung.


98

Preparation procedure: Camphor is comminuted. White Vaseline is melted over water bath at

40 ºC and then is added to comminuted camphor. Finally, mixture is stirred until cool.

Exercise 2.1.9

Rp.

Mentholi 2.25 Methylis salicylatis 4.5 Vaselini albi ad 50.0 M. f. ung.


Preparation procedure: Menthol and methylis salicylas are comminuted together – creation of

eutectic mixture. White Vaseline is melted over water bath at 40 ºC and then added to eutectic

mixture. Finally, mixture is stirred until cool.

Exercise 2.1.10

Rp.

Sinapis etherolei artificialis 0.5 Mentholi 1.0 Camphorae 3.0 Eucalypti etherolei 0.5 Vaselini albi ad 50.0 M. f. ung.

D. S apply ointment to the skin

Preparation procedure: Sinapis etheroleum, mentol, camphor and eucalyptum etheroleum are

comminuted together – creation of eutectic mixture White Vaseline is melted over water bath

at 40 ºC and then added to eutectic mixture. Finally, mixture is stirred until cool.

Two‐phasesuspensionhydrophobicointments


1. Comminution of drugs (adjusting particle size) – a rough mortar with pestle is used in

the pharmacy, followed by straining through a sieve of appropriate mesh size (if the

drug amount is less than ten grams). When comminuting higher amounts, suitable

99

milling equipment can be used. If there is a combination of several drugs, a

homogenous blend is created after comminution (following straining through the

already adjusted to the appropriate particle size (e.g. sulfur for external use with a

maximum particle size of 40 m). These drugs do not have to be comminuted.

2. Premixing drugs – the premixing of drugs is accomplished with a small amount (1:1,

1:0.5) of liquid paraffin, or a liquid component of ointment base, or, with the ointment

base itself at room temperature, or melted. Some surfactants (usually emulsifiers w/o)

are also suitable. Premixing cannot be carried out in a liquid where the drug may be

more soluble than when in the ointment base. This is to avoid any subsequent

recrystallization. with the resulting particles irregularly distributed and their size

exceeding the permitted level. The aim of this operation is to prevent the emergence of

clusters of drug particles, and aid in the preparation of more finely powdered drugs.

When incorporating small quantities of drugs, in order to prevent loss from the

adherence to the walls of the mortar, pestle, and sieve, comminution and premixing is

carried in an oil or ointment base in the mortar.

3. Mixing of the premix suspension with the ointment base – to the premix suspension

is gradually added the ointment base (in parts). Generally, it is desirable to mix

approximately equal amounts (weight) together. If the suspension ointment is prepared

at a higher temperature, the mixture must be stirred until it begins to congeal. Quality

ointments are prepared by diluting the concentrated suspension ointments (e.g. 10%

boric ointment, 50% salicylic ointment, etc.)

Pharmacopoeal ointments: Acidi borici unguentum 10%, Acidi salicylici unguentum 10%,

Jecoris aselli unguentum compositum, Unguentum Whitfield, Zinci oxidi unguentum.

EXAMPLES

Exercise 2.1.11

Acidi salicylici unguentum 10%

Acidum salicylicum (180) 5.0 Paraffinum liquidum 2.5


100

Preparation procedure: Salicylic acid is premixed with liquid paraffin. About 10g of melted

Vaseline is added to this mixture, homogenized, and then the remaining Vaseline is added.

Stir until cool or homogenized.


Dispensing: If the doctor prescribes Acidi salicylici unguentum and does not specify the

concentration, we dispense with 1% ointment. This concentration is adjusted with yellow

Vaseline.

Exercise 2.1.12

Unguentum Whitfield

Acidum salicylicum (90) 2.5 Acidum benzoicum (90) 6.0

Adeps lanae 41.5

Preparation procedure: To the mixture of salicylic and benzoic acid is with constant mixing

added adeps lanae which is melted over a water bath and then stirred until cool.

Storage: Protect from light and store at 8 - 15C.

Exercise 2.1.13

Rp.

Acidi salicylici 1.0 Ung. simplicis ad 50.0 M. f. ung.


Preparation procedure: Acidum salicylicum is premixed with part of the molten base (it is

also possible to premix the drug with sunflower oil, which is added at the expense of

unguentum simplex). With constant mixing, unguentum simplex is added to the mixture,

which is melted over a water bath and then stirred until cool.

101

Exercise 2.1.14

Rp.

Zinci oxidi 10.5 Jecoris aselli olei 15.0 Cerae albae 2.0 Adipis lanae 5.0 Vaselini flavi ad 50.0 M. f. ung.


Preparation procedure: Zincum oxidum is premixed with jecoris aseli oleum. Cera alba,

adeps lanae and White Vaseline are melted over water bath and with constant mixing are

added to the mixture, then stirred until cool.

Exercise 2.1.15

Rp.

Hydrargyri amidochloridi 5.0 Cerae albae 4.0 Adeps lanae 4.5 Vaselini albi ad 50.0 M. f. ung.


Preparation procedure: Hydrargyrum amidochloridum is premixed with a part of the molten

base (it is also possible to premix the drug with liquid paraffin, which is added at the expense

of White Vaseline). Cera alba, adeps lanae and White Vaseline are melted over water bath and

with constant mixing are added the mixture, then stirred until cool.

Ointment must not be prepared in a stainless steel mortar!

102

Exercise 2.1.16

Rp.

Hydrargyri amidochloridi 0.5 Acidi salicylici 0.75 Ung. simplicis ad 50.0 M. f. ung.


Preparation procedure: Hydrargyrum amidochloridum and acidum salicylicum are premixed

with a part of the molten base (it is also possible to premix drugs with sunflower oil, which is

added at the expense of unguentum simplex). Unguentum simplex is melted over a water bath

and with constant mixing is added to the mixture, then stirred until cool.

Ointment must not be prepared in a stainless steel mortar!

Exercise 2.1.17

Rp.

Acidi salicylici 1.0 Lavandulae etherolei 1.0 Syndermani Vaselini flavi. aa ad 50.0 M. f. ung


Preparation procedure: Acidum salicylicum is premixed with a part of the molten base (it is

also possible to premix the drug with liquid paraffin, which is added at the expense of Yellow

Vaseline). Synderman and Yellow Vaseline are melted over a water bath and with constant

mixing are added to the mixture, then stirred until cool. Finally, levandulae etheroleum is

added.

Two‐phaseemulsionhydrophobicointments

Hydrophobic emulsifying ointment bases containing emulsifiers are usually used to prepare

two-phase emulsion ointments. A liquid or drug solution is added to the base (lard) at room

103

temperature while stirring continuously. Generally up to 5% of the drug solution is added to

the base. If the nature of the base requires complete melting (hard paraffin, beeswax, waxy

emulsifiers, etc.), the mixture is stirred until partially cooled, typically to a temperature of

from 40-50C, and then the solution is emulsified into the base. This prevents the excessive

evaporation of water from highly concentrated drug solutions and also the creation of

supersaturated solutions, which are undesirable from the view of stability of the preparation.

Small amounts of concentrated aqueous solutions of drugs (1-2 g) are often added to the

emulsifying ointments and in these cases, in order to avoid significant loss, the drug is

dissolved directly in the mortar, and the resulting solution is added to the ointment base.

Pharmacopoeal ointments: Argenti nitratis unguentum compositum, Ichthamoli unguentum,

Unguentum molle.

EXAMPLES


Exercise 2.1.18

Ichthamoli unguentum

Ichthamolum 5.0 Aqua purificata 2.5

Alcoholum adipis lanae unguentum 42.5

Preparation procedure: Ichthamol is mixed with hot, purified water; after cooling, the purified

water is added to make 15g, and the solution is then gradually incorporated into alcoholum

adipis lanae unguentum.

Storage: Protect from light!

Exercise 2.1.19

Unguentum molle

Adeps lanae 32.5 Paraffinum liquidum 3.75 Vaselinum flavum 25.25

Aqua purificata 5.0

104

Preparation procedure: Adeps lanae, liquid paraffin, and yellow Vaseline are melted over the

water bath, then purified water, pre-heated to 70C is admixed and mixed until cool. Then

water is added to make 100g and after 12 hours the final ointment is mixed.

Storage: Protect from light and store at 8 - 15C.

Dispensing: Before using or dispensing, the ointment must be stirred.

Examples of formulas

Exercise 2.1.20

Rp.

Argenti nitratis 0.5 Aq. purificatae 0.5 Adipis lanae 1.5 Balsamum peruvianum 5.0 Ricini oleum 5.0 Vaselinum flavum ad 50.0 M. f. ung.


Preparation procedure: Yellow Vaseline and adeps lanae are melted over water bath.

Argentum nitras is dissolved in the purified water and then is emulsified into the cooled base.

Balsamum peruvianum is premixed with ricinum oleum (1:1) and this blend is mixed with the

cooled base containing argentum nitras.

Exercise 2.1.21

Rp.

Hydrogenii peroxidi 30% 2.5 Adipis lanae 6.0 Syndermani ad 20.0 M. f. ung.

D. S. Whitening ointment

Preparation procedure: Synderman and adeps lanae are melted over water bath. Hydrogenii

peroxide 30% is emulsified into the cooled base.

105

Exercise 2.1.22

Rp.

Acidi borici 0.075 Aq. purificatae 2.425 Glyceroli 85% 2.5 Adipis lanae 10.0 Vaselini albi ad 50.0 M. f. ung.


Preparation procedure: Vaselinum flavum and adeps lanae are melted over water bath. Cooled

base is mixed with reserve source of acidi borici unguentum 3% (calculate the amount of

reserve source of unguentum acidi borici 3%). Glycerol and purified water are then emulsified

into the base.

Threephasesuspension‐emulsionhydrophobicointments

In the preparation of three-phase hydrophobic ointments, it usually begin by suspending the

solids and hydrophobic parts of the base, including emulsifiers, and thus, a suspension

ointment is created (see the two-phase suspension hydrophobic ointments) in which the

hydrophilic liquid is emulsified (see the two-phase emulsion hydrophobic ointments).

EXAMPLES

Exercise 2.1.23

Rp.

Acidi salicylici Urae aa 2.5 Aq. purificatae 3.5 Syndermani ad 25.0 M. f. ung. D. S. For treating warts

Preparation procedure: Acidum salicylicum is premixed with a part of the molten base (it is

also possible to premix the drug with liquid paraffin, which is added at the expense of

106

synderman). With constant mixing, the rest of synderman is added to the mixture, which is

melted over a water bath and then stirred until cool. Urea is dissolved in purified water and

mixture is finally emulsified into the base by parts.

Exercise 2.1.24

Rp.

Tincturae carbonis detergentis 2.5 Hydrargyri amidochloridi 5.0 Olivae olei 10.0 Aq. purificatae 7.5 Adipis lanae 25.0 M. f. ung.


Preparation procedure: Hydrargyrum amidochloridum is premixed with olive oil. With

constant mixing, adeps lanae is added to the mixture, melted over a water bath and then

stirred until cool. Purified water and tinctura carbonis detergents are then emulsified into the

ointment, separately.

Ointment must not be prepared in a stainless steel mortar!!!!

Exercise 2.1.25

Rp.

Acidi salicylici Ichthamoli aa 1.0 Vaselini flavi Ung. simplicis aa ad 50.0 M. f. ung.


Preparation procedure: Acidum salicylicum is premixed with part of the molten base (it is also

possible to premix the drug with liquid paraffin, which is added at the expense of yellow

Vaseline or with sunflower oil, which is added at the expense of unguentum simplex). Yellow

Vaseline and unguentum simplex are melted over a water bath together and with constant

107

mixing are added to the mixture, then stirred until cool. Finally, ichthamol is emulsified into

the ointment.

Exercise 2.1.26

Rp.

Amyli tritici 2.5 Zinci oxidi 2.5 Jecoris aselli olei 10.0 Adipis lanae 7.5 Aq. purificatae 5.0 Vaselini albi 22.5 M. f. ung.


Preparation procedure: Wheat starch and zinc oxide are premixed with fish oil. White

Vaseline and adeps lanae are melted over water bath and with constant mixing are added to

the mixture, then stirred until cool. Finally, purified water is emulsified into the ointment.

Exercise 2.1.27

Rp.

Argenti nitrici 0.5 Aq. purificatae 0.5 Ung. acidi borici 10% ad 50.0 M. f. ung.


Preparation procedure: Argentum nitricum is dissolved in the purified water and this solution

is emulsified into unguentum acidi borici 10%.

Eye ointments

Eye ointments are prepared according to different principles in the preparation of ointments.

The particular technological process is chosen depending on which form the drug is added

into the ointment (dissolved, suspended, emulsified). Emulsion eye ointments are the most

commonly prepared ointments in the pharmacy. The difference between them and other

108

products is the conditions under which they are prepared (see Basic requirements for the

preparation of liquid preparations - sterile preparations).

EXAMPLES

Exercise 2.1.28

Rp.

Pilocarpini hydrochloridi 0.2 Aq. sterilisatae 0.2 Ung. ophthalmici simpl. ad 10.0 M.f.ung.

D.S. Eye ointment in both eyes before sleeping.

Preparation procedure: Pilocarpinum hydrochloridum is dissolved in sterile water and this

solution is emulsified into the molten base with the same temperature.

Exercise 2.1.29

Rp.

Dexamethasoni 0.01 Propylenglycoli 0.1 Ung. ophthalmici simpl. ad 10.0 M.f.ung.

D.S. Eye ointment in both eyes before sleeping.

Preparation procedure: Trituration of dexamethasone in propyleglycole is emulsified into the

molten base with the same temperature (calculate amount of dexamethasone trituration).

Hydrophilic ointments are prepared from liquid and solid polyethylene glycol melted at

approximately 70C and stirred until cool. When preparing the solution ointments, thermo-

stable drugs are added directly into the melt base, heat-labile drugs are added into semi-cooled

ointment base. When preparing suspension ointments, comminuted solids are premixed with a

melted polyethylene glycol ointment, a liquid polyethylene glycol may be used. The

preparation of an emulsion hydrophilic ointment is the same as for hydrophobic emulsion

ointments.

109

EXAMPLES Hydrophilic ointments

Exercise 2.1.30

Macrogoli unguentum

Macrogolum 300 25.0

Macrogolum 1500 25.0

Both types of polyethylene glycols are melted at a temperature of about 70C and the mixture

is stirred until cool. If the consistency of the prepared ointments is not suitable (consistency of

white Vaseline), it is allowable to change the prescribed amount of polyethylene glycol by up

to 10%.


Exercise 2.1.31

Rp.

Camphorae 1.0 Ung. macrogoli ad 50.0 M. f. ung.


Exercise 2.1.32

Rp.

Methylis salicylatis 0.75 Mentholi 1.0 Eucalypti etherolei 0.25 Ung. macrogoli ad 50.0 M. f. ung.


110

2.2 Creams

Hydrophobic cream bases without drugs

To prepare oleo-creams, an emulsifying base containing emulsifiers w/o is usually used. A

mixture of all prescribed hydrophilic liquids is added to a melted mixture of prescribed

hydrophobic substances with emulsifiers, eventually to emulsifying bases available on the

market (e.g. cetyl alcohol ointment), and both phases should be the same temperature (usually

50-80C) and stirred until cool. When preparing oleo-cream base for storage, the cream must

be stirred again after 24 hours.

Pharmacopoeal creams: Adeps lanae cum aqua, Alcoholis cetylici cremor, Alcoholum adipis

lanae cremor, Cremor refrigerans.

EXAMPLES


Exercise 2.2.1

Adeps lanae cum aqua

Adeps lanae 75.0


Preparation procedure: Water at the same temperature as the base is added to the melted adeps

lanae and stirred until cool.

Storage: At 25C or lower.

Exercise 2.2.2

Alcoholis cetylici cremor

Alcoholis cetylici unguentum 30.0


Preparation procedure: Water at the same temperature as the base is added to the melted cetyl

alcohol ointment and stirred until cool.

Storage: Protect from light and freezing temperatures.

111

Exercise 2.2.3

Alcoholum adipis lanae cremor

Alcoholum adipis lanae unguentum 25.0


Preparation procedure: Water with the same temperature as the base is added to the melted

ointment from wool grease alcohol and stirred until cool.


Exercise 2.2.4

Cremor refrigerans

Cera alba 4.0 Cetylis palmitas 5.0 Helianthi oleum raffinatum 28.5 Natrii laurylsulfas 0.05 Aqua purificata 10.0 Ricini oleum virginale 2.5 Methylparabenum 0.02 Propylparabenum 0.005 Propylis gallatis 0.01

Geranii etheroleum 0.15 ml

Preparation procedure: White wax, cetyl palmitate, sunflower oil, sodium lauryl sulphate and

castor oil are melted over a water bath. Propyl gallate is dissolved into the melted mixture.

Parabens are dissolved in the water at the same temperature (about 50 C) and then are

admixed gradually into the melted base, then is stirred until cool. Finally, geranium essential

oil is added to the cooled cream.


Labeling: Display antimicrobial agents on the label!

112

Exercise 2.2.5

Rp.

Cerae albae 5.0 Cetacei 5.0 Glyceroli monostearatis 2.5 Helianthi olei 25.0 Ricini olei 2.5 Propylis gallatis 0.01 Aq. purificatae 10.0 Mehylparabeni 0.035 Propylparabeni 0.015 Geranii etherolei III guttae M. f. cremor

D. S. apply cream to the skin

Preparation procedure: White wax, cetyl palmitate, glycerol monostearas, sunflower oil, and

castor oil are melted over a water bath. Propyl gallate is dissolved into the melted mixture.

Parabens are dissolved in the water at the same temperature (about 50 C) and then are

admixed gradually into the melted base, then is stirred until cool. Finally, geranium essential

oil is added to the cooled cream.

Exercise 2.2.6

Rp.

Cerae albae Cetacei Adipis lanae aa 3.75 Helianthi olei 20.0 Cholesteroli 0.75 Natrii tetraboratis 0.225 Aq. purificatae 17.75 M. f. cremor


113

Preparation procedure: White wax, cetaceum, adeps lanae, sunflower oil and cholesterol are

melted over a water bath. Then, sodium tetraborate dissolved in warm water is added while

stirring slowly.

Exercise 2.2.7

Unguentum leniens

Cera alba 4.0 Cetaceum 7.5 Helianthi oleum 25.0 Ricini oleum 5.0 Natrii tetraboras 0.25 Aq. purificata 8.25

Geranii etherolei III guttae

Preparation procedure: White wax, cetaceum, sunflower oil and castor oil are melted over a

water bath. The mixture is allowed to stay in the mortar without stirring until cool. The stiff

base is spread to the foam with light pressure. Then, sodium tetraborate dissolved in warm

water is added while stirring slowly. Finally, geranium essential oil is added to the cooled

cream.

Hydrocream bases without drugs

Hydrocreams are distinguished according to the presence of emulsifiers:

Stearin hydrocreams – are stabilized by an ionic emulsifier (soap), which is result of

in situ neutralization of stearin by an excess of the appropriate alkali (hydroxide or

carbonate sodium, potassium, ammonium, trolamine), usually by heating over a water

bath.

Hydrocreams stabilized by a complex emulsifier – are stabilized by a combination

of emulsifiers o/w or w/o in the appropriate ratio, which are designated complex

emulsifiers. Usually, they are prepared at a temperature of 65-80 C by English (wet

gum) or Continental (dry gum) technique. English technique is used when the

individual emulsifiers are available: the emulsifier w/o is heated with other

hydrophobic components over a water bath until completely melted, forming a

homogeneous mixture. A solution of the emulsifier o/w is prepared in another vessel

114

with hydrophilic components. These two phases are then mixed together, stirred until

the cream has cooled while continuously scraping the mixture from the walls of the

mortar. The Continental technique is used when a mixture of emulsifiers (w/o and

o/w) are available. The mixture of emulsifiers is heated with hydrophobic substances,

and then the water phase at the same temperature is added gradually and stirred until

cool.

Pharmacopoeal ointments: Cremor anionicus, Cremor nonionicus.

EXAMPLES


Exercise 2.2.8

Cremor nonionicus

Unguentum emulsificans nonionicum 20.0 Propylenglycolum 5.0 Aqua purificata 25.0 Methylparabenum 0.05

Propylparabenum 0.025

Preparation procedure: A warm solution of parabens in a mixture of propylene glycol and

purified water at the same temperature is added to the nonionic emulsifying ointment melted

over a water bath at 70C and stirred until cool. Purified water is admixed to the cold cream to

100g.



115

Exercise 2.2.9

Rp.

Kalii carbonatis 0.5 Cetacei 1.0 Stearini 6.25 Glyceroli 85% 10.0 Aq. conservantis 32.2 Lavandulae etherolei 0.05 M. f. cremor

D. S. Hand cream

Preparation procedure: Potassium carbonate is dissolved in a beaker in water with

preservatives; glycerol is then added and heated until boiling. An aqueous solution is added to

the melted cetaceum and stearin while continuously stirring. The mixture is kept over a

boiling water bath for approximately 30 min. while continuously adding evaporated water.

After removing the mixture from the water bath evaporated water is again added and the

mixture is vigorously stirred until cool (do not cool down quickly due to the creation of grainy

cream).

Exercise 2.2.10

Rp.

Neoaquasorbi 25.0 Glyceroli 85% 5.0 Aq. conservantis 20.0 M. f. cremor


Preparation procedure: Neoaquasob, glycerol and purified water are melted over water bath.

Cream is then stirred until it has cooled, with continuous scraping of the mixture from the

walls of the mortar.

116

Exercise 2.2.11

Rp.

Stearini 7.5 Adipis lanae 1.0 Paraffini liquidi 12.5 Trolamini 1.0 Glyceroli 85% 2.5 Aq. purificatae ad 50.0 M. f. cremor

D. S. apply cream on the skin

Preparation procedure: Stearin, adeps lanae and liquid paraffine are melted over a water bath.

Trolamin, glycerol and water are heated up in the beaker with the same temperature as the

cream base. Both phases are then mixed together at the same temperature and stirred until

cool, with continuous scraping of the mixture from the walls of the mortar.

Oleocreams and hydrocreams with drugs

Two-phase cream – the drug is dissolved in the phase that is soluble, then is continued as in

the preparation of the corresponding type of cream. Liquid drugs that are miscible with the

outer phase of the cream can be stirred into the finished cream. Volatile substances are then

added to the cold cream.

Three-phase cream - contains drugs that are insoluble in any phase of the cream. The

comminuted drug or mixture of drugs is premixed with the part of the cream base or the liquid

that is miscible with the outer phase of the cream, and then the rest of the cream is added. In

the preparation of three-phase oleocream containing less of the aqueous phase (up to 20%) at

room temperature (e.g. hydrophobic base Synderman allows for emulsification at room

temperature) it is possible to apply the principles of three-phase hydrophobic ointment

preparation, i.e., the hydrophobic suspension ointment is prepared in which the prescribed

amount of hydrophilic liquid is emulgated.

Pharmacopoeal ointments: Aluminii acetotartratis cremor.

117

EXAMPLES


Exercise 2.2.12

Aluminii acetotartratis cremor

Aluminii acetotartratis solutio 5.0 Aqua purificata 5.0 Adeps lanae 10.0


Preparation procedure: Adeps lanae and yellow Vaseline is heated over a water bath at 40C

and homogenized. The mixture of aluminii acetotartratis solution and purified water (40C) is

then mixed gradually into the melted base. The mixture is then stirred until cool. After 24

hours the ointment is re-mixed.


EXAMPLES

Exercise 2.2.13

Rp.

Geranii etherolei 1.0 Adipis lanae cum aq. 1.5 Acidi borici sol. 3% 12.5 Helianthi olei 12.5 Syndermani ad 50.0 M. f. cremor


Preparation procedure: Adeps lanae cum aqua, sunflower oil and synderman are melted over a

water bath. Then, solution of boric acid heated to the same temperature as the base is added to

the base and stirred until cool with continuous scraping of the mixture from the walls of the

mortar. Finally, geranium essential oil is added to the cooled cream.

118

Exercise 2.2.14

Rp.

Acidi salicylici 1.0 Aq. purificatae 19.0 Neoaquasorbi ad 50.0 M. f. cremor


Preparation procedure: Neoaquasor is mixed with purified water over water bath. Salicylic

acid is then suspended into the base.

119

2.3 Gels

Gels are prepared due to the swelling of the polymers. Preparation is not uniform, since

different substances require different conditions for swelling, dissolution and gelation (sol-gel

transition). Generally, they are prepared by layering finely-powdered gelling agents on a

liquid surface at room temperature. For substances that can very easily form clumps, which

makes swelling difficult, it is sometimes recommended to premix the gelling agents with

alcohol or glycerol.


1. Gels prepared at room temperature - from tragacanth, methyl cellulose, povidone,

etc.

2. Gels prepared at higher temperature - agar, starch, gelatin, sodium salt of carmellose

3. Gels prepared by neutralization (change pH) - polyacrylic acid (carbomers).

Pharmacopoeal gels: Glyceroli unguentum, Zinci oxidi gelatina mollis.

EXAMPLES


Exercise 2.3.1

Zinci oxidi gelatina mollis

Zinci oxidum (125) 10.0 Glycerolum 85% 40.0 Gelatina 15.0

Aqua conservans 35.0

Preparation procedure: Gelatin is uniformly wetted by water with preservatives and is

allowed to swell for 15 minutes. The mixture is then heated over a water bath at a temperature

not exceeding 65C until the gelatin dissolves. The evaporated water is replaced by warm

purified water and the comminuted mixture of zinc oxide is mixed into the gelatin solution

with 85% glycerol. The warm mixture is then poured into a wide-necked bottle.

120


Exercise 2.3.2

Glyceroli unguentum

Glycerolum 85% 90.0 Methylparabenum 0.2 Ethanolum 96% (V/V) 1.0 Tritici amylum (125) 10.0


Preparation procedure: The modified procedure - glycerol is heated to approximately 90°C.

Wheat starch is then mixed with water and a methylparaben solution in alcohol. The mixture

is then heated over a water bath, while constantly being stirred until the mixture thickens -

homogeneous translucent ointment is then created. The evaporated water is refilled and stirred

until cool.



Examples of formulas

Exercise 2.3.3

Rp.

Carbopoli 0.25 Natrii hydroxidi sol.10% q.s. Sol. methylthionii chloridi 1% 1 gtt I Aq. purificatae ad 50.0 M. f. gel

D. S. Lubricant

121

Exercise 2.3.4

Rp.

Urae 2.5 Carbopoli 0.25 Glyceroli 85% 5.0 Trolamini q.s. Aq. purificatae ad 50.0 M. f. gel

D. S. Urea gel

Preparation procedure: Note for tasks 3 and 4: the gel is prepared by layering Carbopol at

approximately half the amount on the surface of the water (in the mortar), and after the

swelling it is stirred to a smooth mixture. The gel is prepared by adding (neutralization) the

appropriate alkali drops. Then the remaining water (or the aqueous solution of the drugs and

other substances) is added to the mixture.

Exercise 2.3.5

Gelatum gelatinae

Gelatina 10.0

Aq. conservans 90.0

Preparation procedure: Gelatin is added to the beaker with water with preservatives and is

allowed to swell for 15 minutes. By heating over a water bath (70 C) the gelatin is dissolved

(do not boil!!!). Evaporated water is added with hot purified water, and the solution is then

poured into a wide-necked bottle, closed and allowed to cool.

Exercise 2.3.6

Gelatum agari

Agarum 1.0

Aq. conservans 99.0

Preparation procedure: Agar with preservative water (without swelling) is heated on the

cooker to a boil and is boiled until agar is dissolved. Evaporated water is added with the hot

122

purified water, and then the solution is poured into a wide-necked bottle, closed and allowed

to cool.

123

2.4 Pastes

Pastes are prepared according to the same principles as suspension or three-phase ointments,

the difference being that the hydrophobic base is completely melted for easy preparation.

When a cream base is used for preparing paste, especially hydrophilic cream (e.g.

Ambiderman), it is used from premixing of the solids.

Pharmacopoeal pasta: Sulfuris pasta 50%, Sulfuris pasta composita, Zinci oxidi pasta, Zinci

oxidi pasta 50%, Zinci oxidi pasta salicylata.

Examples of pharmacopoeal formulas

Exercise 2.4.1

Sulfuris pasta composita

Sulfur ad usum externum 20.0 Kalii carbonas 10.0 Sapo kalinus 15.0


Sulphur for external use and potassium carbonate are mixed together. The mixture is first

mixed with potassium soap (sapo kalinus), and then is gradually admixed to the melted

Vaseline.


Exercise 2.4.2

Zinci oxidi pasta

Zinci oxidum (125) 25.0 Tritici amylum (125) 25.0


Preparation procedure: A mixture of dried zinc oxide and wheat starch are strained through a

sieve, and are thoroughly comminuted in a warm stainless steel mortar with melted yellow

Vaseline and then mixed until cool.


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Exercise 2.4.3

Zinci oxidi pasta mollis

Zinci oxidum (125) 30.0 Helianthi oleum raffinatum 20.0 Alcoholes adipis lanae 5.0


Preparation procedure: Zinc oxide is thoroughly comminuted with sunflower oil. The melted

mixture of alcohols adipis lanae and yellow Vaseline is gradually admixed to the obtained

suspension , and stirred until cool.


Exercise 2.4.4

Zinci oxidi pasta salicylata

Acidum salicylicum (90) 2.0 Vaselinum flavum 2.0

Zinci oxidi pasta 96.0

Preparation procedure: Salicylic acid is thoroughly comminuted with melted yellow

Vaseline, and is gradually admixed into zinc paste.


Examples of formulas:

Exercise 2.4.5

Rp.

Bismuthi subgallatis 17.0 Zinci oxidi 20.0 Tritici amyli 20.0 Helianthi olei 18.0 Adipis lanae cum aq. 25.0 M. f. pasta

D. S. Schmiden pasta

125

Preparation procedure: Bismuth subgallas, zinc oxide and wheat starch are premixed with

sunflower oil. Adeps lanae cum aqua is melted over water bath, gradually admixed to the

obtained suspension, and stirred until cool.

Exercise 2.4.6

Rp.

Picis lithantracis 1.5 Zinci oxidi Talci aa 15.0 Cremoris Neoaquasorbi ad 100.0 M. f. pasta

D. S. apply pasta to the skin

Preparation procedure: Pix is dissolved in about 5g of ether. Dissolved pix is then mixed with

powders of zinc oxide and talc. Finally, Neoaquasorb cream is gradually admixed to the

mixture.

ISBN 978-80-7305-671-1

Autors: Kateřina Dvořáčková

Aleš Franc

Jan Gajdziok

Martina Kejdušová

David Vetchý

Title: MEDICAL PHORMS AND BIOPHARMACY

I.Liquid and semi-solid drugs

Department: Department of Pharmaceutics

Pages: 125

Edition: 1st

Publisher: University of Veterinary and Pharmaceutical Sciences Brno

Documents

MEDICAL FORMS AND BIOPHARMACY - VFUsis.vfu.cz/links/dvorackovakaterina-medical-forms-and-biopharmacy... · 1.5 Aromatic waters ... The aim of these practical classes from subject