KAUSAR AHMAD KULLIYYAH OF PHARMACY Cream Formulation 1 PHM4153 Dosage Design 2 2011/12

KAUSAR AHMADKULLIYYAH OF PHARMACY

Cream Formulation

http://staff.iium.edu.my/akausar

1

PHM4153 Dosage Design 2 2011/12

http://staff.iiu.edu.my/akausar

Contents


Ideal formulatio

n

Types of excipients Properties

2

Examples of Creams


• Benzophenone, hydroquinone

• Fruit extracts

Whitening

• Collagen, seaweed extract • Liposome

Anti-ageing

• Fish• Herbs Virility

3

Formulation


Process whereby drugs are combined with other substances (excipients)• e.g. preservative

to produce dosage forms

• e.g. cream

suitable for administration to or by patients.

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Ideal formulation


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Non-irritant Non-allergenic Non-staining

Easy to apply Pleasant

feeling to the skin

Non-toxic

Non-harmfulIncapable of microorganis

m growth

Free from side-effects

Formulation requirement: efficacy, safety, and quality


Contain accurate dose

Convenient to take or

administer

Provide drug in a form for

absorption or other delivery to

the target

Retain quality throughout shelf life &

usage period

Manufactured by a process that does not compromise performance and

that is reproducible and economical

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Factors to be considered in formulation


Physicochemical properties

• Waxes and oils or emulsions

Choice of vehicle

• Provide essential part of the dosage form• Prevent degradation of the formulation

Categories of excipients

Stability

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Choice of vehicle


Bases from mixtures of

low and high MW PEG

Liposomes Microemulsions

Multiple emulsions

Fluorocarbon emulsions – ultra low i

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Examples of Oils & Fats


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• Cyclomethicones• DimethiconesSilicones

• Castor oil• Glyceryl tricaprylate

Triglycerides/ vege oils

• Octyl stearate• Isopropyl palmitate

Simple esters

Advantages of Silicones


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Chemical and physical• stable, colourless, odourless

Cosmetic• Skin-feel, gloss/matte

Dermo-toxicology• Not sensitizing, non-comedogenic,

Examples of Lipids


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• Mineral oilHydrocarbons

• BeeswaxWax

• Dicaprilyl etherEther

• Cetyl alcoholAlcohols

• Stearic acidAcids

Properties Limitation


Emollient effectShineLubricitySpreadabilitySolvencyDrying

OdourColourViscosityMiscibility with

other oilsToxicityImpuritiesCost

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Choosing Oils

Non-polar Polar


Lasting emollient effect

Barrier effectInertStable against

oxidationShineSpreadabilitycheap

Varying emollient effect

Little barrier effectVarying stability

against oxidationGood absorptionGood deliveryexpensive

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Polarity of oils

Excipients


Other components other than API added to formulation

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Categories of excipients


Provide essential parts of dosage form & enhance bioavailability

• Emulsifiers• Viscosity modifier

Prevent degradation of the formulation: protect, improve safety & enhance stability

• Anti-oxidants• Anti-bacterials• Preservatives• UV absorbers

Aid processing during manufacturing

Assist product identification colour

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Choosing excipients


physiological inertness

physical and chemical stability

conformance to regulatory

agency requirements

no interference with drug

bioavailability

absence of pathogenic microbial

organisms

commercially available at

low cost

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Emulsifiers


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w/o

o/w

Penetration enhancers


Disturb packing of SC lipid bilayer• Examples: surfactants

Disruption of skin barrier • Extraction of skin lipids with apolar solvents e.g.

acetone• Physical stripping

• Physically or chemically induced irritation

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Increase delivery of active substance by:

Hydration


Hygroscopic effect

NaCl Sorbitol

PPG glycerol

Alter water-binding capacity of corneocytes

Low MW glycerol

s

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Q. How does urea moisturise the skin?


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pH adjustment


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Triethanolamine

NaoH

Preservatives


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Sodium methyl/butyl/propyl paraben

Imidazolidinyl urea

Anti-oxidant


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Butyl hydroxy tolueneButyl hydroxy anisole

UV filters


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Zinc oxide

Titanium dioxide

Benzophenone

Other types of excipients


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Soothing•Allantoin

Anti-free radicals•Polyphenols

Effects of excipients


texture and consistency

phase behaviour of the component

emulsifiers.

physicochemical properties

rheological, thermal and

microscopical

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Physicochemical properties


Oils susceptible to oxidation

Add antioxidants• E.g. BHT, BHA

Aqueous solutions support microbial

growth

Add preservatives• E.g. methyl and

propyl paraben• BUT these

may affect the endocrine…..

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Physical and chemical properties of excipients


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solubility hygroscopicity swelling hydration

capacity

particle size distribution

bulk & tap density

specific surface area

complexation

infrared spectrum microbes


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10 m, porous

7 m, empty spheres

Polyamide: Carrier for insoluble ingredients; Protector for sensitive ingredients; Slow delivery & long lasting effect

Excipient: Particle size distribution


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Excipient: Pore volume & pore diameter


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Incompatibility


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Chemical

pH/dissociation

pH/disperse systems

polyvalent cations

complexation

cationic and anionic compounds of high MW

reducing agents (cause fading of dyes)

Physical

Immiscibility

Insolubility

Packaging

Formulation and packaging materials

Detection of Incompatibility


Cracked cream

Hydrolysis or

oxidation

Discoloration

Precipitation

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Effect of type of preparation: Absorption of retinyl palmitate


Exercise:

18% absorbed from acetone vehicle

compared to only

4% absorbed from o/w emulsion

Q WHY?

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Exercise: Determine functions of excipients


Nizoral creamKetoconazolePPGStearyl alcoholCetyl alcoholSorbitan stearatePolysorbate Isopropyl myristateSodium sulfitePurified water

Elomet cream 0.1%Mometasone furoateWhite petrolatumWhite waxPPG stearateStearyl alcoholCeteareth-20Hexylene glycolTitanium dioxideAl starch

octenylsuccinatePurified waterPhosphoric acid

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References


Bugay, D. E. (1999). Pharmaceutical excipients : characterization by IR,

Raman, and NMR spectroscopy.

RS201E87B931P

Kibbe, A. H. (2000). Handbook of pharmaceutical excipients.

RS201E87H236K

Rowe, R. C., Sheskey, P. J. & Owen, S. C. (2006). Handbook of

pharmaceutical excipients

RS201E87H236K

Rowe, R. C. (2009). Handbook of pharmaceutical excipients.

RS201E87H236K

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Some materials sourced from the following:

http://www.eastman.com/Markets/Pharmaceutical/Excipients/Excipients_intro.asp

http://www.pharmaceutical-technology.com/contractors/materials/uniqema/

http://www.pformulate.com/

http://images.vertmarkets.com/CRLive/files/Downloads/89FB7970-7376-44A0-B6B6-4B171E4B978B/InsolubleKollidon.pdf

Thank you to contributors.



http://www.pharmaceutical-technology.com/contractors/materials/uniqema/

http://www.pformulate.com/



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KAUSAR AHMAD KULLIYYAH OF PHARMACY Cream Formulation 1 PHM4153 Dosage Design 2 2011/12