Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Dosage Form Design: Pharmaceutical and Formulation
Considerations Chapter 4
Slide 2
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Objectives After reading this chapter, the student
will be able to: 1.List reasons drugs are incorporated into various
dosage forms. 2.Compare and contrast the advantages/disadvantages
of various drug dosage forms. 3.Describe the information needed in
preformulation studies to characterize a drug substance for
possible inclusion into a dosage form. 4.Describe the mechanisms of
drug degradation and provide examples of each. 5.Describe the five
types of drug instability of concern to the practicing pharmacist.
6.Summarize approaches employed to stabilize drugs in
pharmaceutical dosage forms. 7.Calculate rate reactions for various
liquid dosage forms. 8.Categorize various pharmaceutical
ingredients and excipients.
Slide 3
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Dosage Form Design: Pharmaceutical and Formulation
Considerations The need for dosage forms General considerations in
dosage form design Pharmaceutical ingredients and excipients
Slide 4
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins General Considerations in Dosage Form Design
Preformulation Studies Physical Description Microscopic Examination
Heat of Vaporization Melting Point Depression The Phase Rule
Particle Size Polymorphism
Slide 5
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins General Considerations in Dosage Form Design (contd)
Preformulation Studies (contd) Solubility Solubility and Particle
Size Solubility and pH Dissolution Membrane Permeability Partition
Coefficient pKa/Dissociation Constants
Slide 6
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins General Considerations in Dosage Form Design (contd)
Drug and Drug Product Stability Drug Stability: Mechanisms of
Degradation Drug and Drug Product Stability: Kinetics and Shelf
Life Rate Reactions Q 10 Method of Shelf Life Estimation Enhancing
Stability of Drug Products Stability Testing
Slide 7
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Pharmaceutical Ingredients and Excipients Definitions
and Types Handbook of Pharmaceutical Excipients Harmonization of
Standards Appearance and Palatability Flavoring Pharmaceuticals
Sweetening Pharmaceuticals Coloring Pharmaceuticals
Slide 8
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Pharmaceutical Ingredients and Excipients (contd)
Preservatives Sterilization and Preservation Preservative Selection
General Preservative Considerations Mode of Action Preservative
Utilization
Slide 9
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins The Need for Dosage Forms
Slide 10
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins The Need for Dosage Forms Mechanism for safe and
convenient delivery of accurate dosage Protection of drug from
atmosphere Protection of drug from gastric acid (EC) Conceal
bitter, salty, or offensive taste or odor Provide liquid
preparations of insoluble drugs
Slide 11
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins The Need for Dosage Forms (contd) Provide clear
liquid dosage forms (solutions) Provide rate-controlled drug action
Provide topical drug action (ointments, creams, patches,
ophthalmic, otic, nasal) Provide for insertion into body cavity
Provide for placement into bloodstream Provide for inhalation
therapy
Slide 12
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins General Considerations in Dosage Form Design
Slide 13
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Physiological States Altering Response to Drugs Age
(infants) Age (elderly) Diurnal variation Pregnancy Sex Menopause
Race Body weight Time of administration Tolerance Temperature
Physiological reserve Milieu
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Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Factors Affecting Drug Presentation to the Body
Portal of drug entry into the body Physical form of the drug
product Design and formulation of the product Method of manufacture
of the product Physicochemical properties of the drug and
excipients
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Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Factors Affecting Drug Presentation to the Body
(contd) Physicochemical properties of the drug product Control and
maintenance of location of drug at the absorption site Control of
the release rate of the drug from the drug product
Slide 16
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Design of Drug Products Effectiveness Safety
Reliability Stability Physical Chemical Microbiological
Slide 17
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Design of Drug Products (contd) Pharmaceutical
elegance Appearance Organoleptic properties Convenience Ease of use
Dosing frequency Consumer acceptance
Slide 18
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins General Considerations in Dosage Form Design
Preformulation Studies Drug and Drug Product Stability
Slide 19
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Preformulation Studies Chemical characterization
Physical characterization
Slide 20
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Physical Description Solids, liquids, gases Chemical
Properties Structure, form, reactivity Physical Properties
Description, particle size, crystalline structure, melting point,
solubility Biological Properties Ability to get to site of action
and elicit a response
Slide 21
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Microscopic Examination Particle size Particle size
range Crystal structure Particle shape
Slide 22
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Heat of Vaporization Vapor pressure Volatile drugs
can migrate within a solid dosage form Personnel exposure
Slide 23
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Melting Point Depression Purity determination
Identity
Slide 24
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins The Phase Rule Phase diagrams Visual picture of
presence of solid and liquid phases in binary, ternary, and other
mixtures
Slide 25
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Particle Size Dissolution rate Bioavailability
Content uniformity Taste Texture Color Stability Flow
characteristics Sedimentation rates
Slide 26
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Polymorphism Crystalline Amorphous Melting point
variation Solubility differences
Slide 27
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Solubility Some aqueous solubility required for
therapeutic efficacy Equilibrium solubility Solubility in different
solvents
Slide 28
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Solubility and Particle Size Small increases in
solubility can be achieved by particle size reduction. Decreases in
particle size may enhance dissolution rates.
Slide 29
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Solubility and pH pH:solubility profiles are
important. pH can affect solubility.
Slide 30
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Dissolution Dissolution may be rate-limiting step in
the absorption of poorly soluble drugs. Can affect onset,
intensity, and duration of response and control overall
bioavailability of the drug from the dosage form
Slide 31
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Membrane Permeability pKa, solubility, and
dissolution rate data can provide an indication of absorption.
Slide 32
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Partition Coefficient Octanol:water partition
coefficient often used in formulation development
Slide 33
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins pKa/Dissociation Constants Extent of dissociation or
ionization Dependent on pH of medium Can affect absorption,
distribution, and elimination
Slide 34
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Drug and Drug Product Stability Physical stability
Chemical stability Shelf life of 2-3 years is generally
desired
Slide 35
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Drug Stability: Mechanisms of Degradation Hydrolysis,
solvolysis Oxidation Other processes
Slide 36
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Drug and Drug Product Stability: Kinetics and Shelf
Life Chemical stability Physical stability Microbiological
stability Therapeutic stability Toxicologic stability
Slide 37
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Rate Reactions Change of drug concentration with
respect to time
Slide 38
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Q 10 Method of Shelf Life Estimation Shelf life
estimation Q 10 = e {(Ea/R)[(1/T + 10) (1/T)]}
Slide 39
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Enhancing Stability of Drug Products Excipients may
be added to protect the drug Antioxidants Preservatives Chelating
agents Buffering agents
Slide 40
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Stability Testing Done at each stage of product
development Product containers and closures must be considered
Temperature and humidity studies Light studies Changes in physical
appearance, color, odor, taste, texture Chemical changes of drug
degradation Pharmacist is last professional to check for quality
and stability prior to dispensing
Slide 41
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Kinetics and Drug Stability Kinetics is important in
all phases of the drug development process as well as in quality
control, stability, bioavailability, and therapeutic drug
monitoring.
Slide 42
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Kinetics The study of the rate of chemical change and
the way this rate is influenced by conditions of concentration of
reactants, products, and other chemical species that may be present
and by factors such as solvent, pressure, and temperature
Slide 43
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Importance of Kinetics 1. Selection of proper storage
temperature Temperature Light Advising patient on storage
conditions 2. Selection of proper container for dispensing Glass
vs. plastic Clear vs. amber vs. opaque Cap liner selection
Slide 44
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Importance of Kinetics (contd) 3. Anticipation of
interactions when mixing drugs and dosage forms (incompatibilities)
Active drugs Excipients 4. Dissolution determinations
Slide 45
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Importance of Kinetics (contd) 5. ADME Processes in
pharmacokinetics A = Absorption D = Distribution M =
Metabolism/Biotransformation E = Excretion 6. Drug action at the
molecular level
Slide 46
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Responsibility of the Pharmacist Dispense oldest
stock first and observe expiration dates. Store products under
conditions stated in USP monographs and/or labeling. Observe
products for evidence of instability. Properly treat/label products
that are repackaged, diluted, or mixed with other products.
Slide 47
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Responsibility of the Pharmacist (contd) Dispensing
in proper container with proper closure Informing/educating
patients concerning proper storage and use of products, including
the disposition of outdated or excessively aged prescriptions
Slide 48
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Why Do We Need Shelf Life Estimates? Expiration date
given at room temperature: What is the expiration extension if
refrigerated? Expiration date for refrig temperature given: How
long if left at room temperature? Expiration date for room
temperature given and it is desired to heat (autoclave): What is
the % decomposition?
Slide 49
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Why Do We Need Shelf Life Estimates? (contd)
Expiration date for refrigerated temperature given; product stored
at room temperature and then returned to refrigerator: What is the
new expiration date?
Slide 50
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Stability: USP The extent to which a product retains,
within specified limits, and throughout its period of storage and
use (i.e., its shelf life), the same properties and characteristics
that it possessed at the time of manufacture
Slide 51
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Definitions Accelerated Testing Studies designed to
increase the rate of chemical or physical degradation by using
exaggerated storage conditions Bulk Drug Substance Active drug
before formulation Drug Product Finished dosage form
Slide 52
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Definitions (contd) Expiration Date The date placed
on the immediate container label of a drug product that designates
the date through which the product is expected to remain within
specifications Expiration Dating Period The interval that a drug
product is expected to remain within the approved specifications
after manufacture
Slide 53
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Definitions (contd) Primary Stability Data Data on
the drug product stored in the proposed container-closure for
marketing under storage conditions that support the proposed
expiration date
Slide 54
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Definitions (contd) Stability-Indicating Methodology
Quantitative analytical methods based on the characteristic
structural, chemical, or biological properties of each active
ingredient of a drug product, and that will distinguish each active
ingredient from its degradation products so that the active
ingredient content can be accurately measured
Slide 55
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Definitions (contd) Stability The capacity of a drug
product to remain within specifications established to ensure its
identity, strength, quality, and purity Strength A quantitative
measure of active ingredient, as well as other ingredients
requiring quantitation Supportive Stability Data Data other than
primary stability data
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Observing Products for Evidence of Instability Solid
Dosage Forms Hard/soft gelatin capsules Uncoated tablets Coated
tablets Dry powders and granules Powders/granules for
solution/suspension Effervescent tablets/granules/powders
Slide 58
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Observing Products for Evidence of Instability
(contd) Liquid Dosage Forms Solutions/elixirs/syrups Emulsions
Suspensions Tinctures/fluid extracts Sterile liquids Semisolids
Creams Ointments Suppositories
Slide 59
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Reaction Kinetics Want two things from kinetic data:
Reaction order Reaction rate In considering the chemical stability
of a pharmaceutical, we need to know the REACTION ORDER, which is
obtained experimentally by measuring the REACTION RATE as a
function of concentration of the degrading drug.
Slide 60
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Reaction Kinetics The overall ORDER of a reaction is
the SUM of the EXPONENTS of the CONCENTRATION terms of the RATE
EXPRESSION. The ORDER with respect to EACH REACTANT is the EXPONENT
of the INDIVIDUAL CONCENTRATION terms in the RATE EXPRESSION.
Slide 61
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Order of a Reaction An experimental quantity; merely
provides information about the way in which the rate depends on
concentration
Slide 62
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Factors Affecting Reaction Rates Temperature
Dielectric Constant Ionic Strength Solvent Effect Catalysis
Light
Slide 63
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Chemical Kinetics vs. Chemical Stability KINETICS
Several half-lives Pure systems Goal is to elucidate reaction
mechanisms. STABILITY Down to about 85% of drug remaining Involves
complete dosage form Goal is to establish an expiration date.
Slide 64
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins First-Order Rate Reaction dt dC = kC
Slide 65
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Half-Life Is meaningless to attempt to describe the
time required for ALL material to decompose (i.e., infinity)
Therefore, reaction rate can be described by K or half- life, t
1/2
Slide 66
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Zero-Order Rate Reaction dC\dt = k 0 C = k 0 t + C
0
Slide 67
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Arrhenius Equation log = k 2 \k 1 = Ea (t 2 T 1 )\2.3
RT 1 T 2
Slide 68
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Arrhenius Equation (contd) Energy of activation
calculations
Slide 69
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Energy of Activation and Reaction Types 2-3
kcal/mole----------
Slide 70
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Shelf Life Estimates Q 10 = [K(T+10)]/KT =e [-(Ea/R)
({1/T+10} - {1/T}] Q 10 =2Lower limit Q 10 = 3Average, best
estimate Q 10 = 4 Upper limit
Slide 71
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins t 90 Equation for Shelf Life Estimates t 90 (T 2 ) =
t 90 (T 1 )/Q 10 (Delta T/10) Note: A + Delta T decreases shelf
life and a - Delta T increases shelf life
Slide 72
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Pharmaceutical Ingredients and Excipients
Slide 73
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Definitions and Types Active pharmaceutical
ingredients Pharmaceutical ingredients added to prepare a dosage
form
Slide 74
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Components of Drug Delivery Systems Drug Route of
administration Suitable physical dosage form Use of chemical
derivatives of the drug Control of certain physicochemical and/or
biochemical processes that alter the rate and extent of
response
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Handbook of Pharmaceutical Excipients Monographs on
more than 250 excipients used in dosage form preparation Additional
excipients listed in Food Chemicals Codex and National
Formulary
Slide 77
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Harmonization of Standards International
harmonization of excipients Pharmaceutical industry is
multinational Uniform standards needed
Slide 78
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Appearance and Palatability Compliance issues Odor,
color, and taste Important for all age groups, especially
pediatrics and geriatrics
Slide 79
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Flavoring Pharmaceuticals Complex area Important for
compliance Color and taste should generally match
Slide 80
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Flavor Taste Touch Smell Sight Sound
Slide 81
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Four Primary Tastes Sweet Bitter Sour Salty
Slide 82
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Four Primary Tastes (contd) TASTESLIGHTMODSTRG
Sweet/Sucrose5%10%15% Sour/Citric Acid0.050.100.20
Salty/NaCl0.40.71.0 Bitter/Caffeine0.050.100.20
Slide 83
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Causative Factors for Taste Hot Mild, counterirritant
Astringent Tannins, acids Coarseness/GrittinessTexture Coolness Neg
heat of solution Greater sensitivity to odors than to tastes
Females have greater sensitivity to odors than males
Slide 84
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Flavor/Odor Correlations with Chemical Structure Sour
tasteH+ SaltinessAnions & cations BitterHigh-MW salts
SweetPolyhydroxyl cmpds, polyhalogenated cmpds, alpha amino acids
Sharp, bitingUnsaturation Camphoraceous odorTertiary C atom
Slide 85
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Flavor/Odor Correlations with Chemical Structure
(contd) Pleasant odorKetones MethylparabenFloral, gauze-pad
Propyl/butyl parabenNumbing mouthfeel
Slide 86
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Flavor Selection Immediate flavor identity Rapid full
flavor development Acceptable mouthfeel Short aftertaste No
undesirable sensations
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Flavoring Techniques (contd) Physical Formation of
insoluble compounds Emulsification of oils Effervescence
High-viscosity fluids Coating tablets
Slide 89
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Flavoring Techniques (contd) Chemical
Adsorption-silica gel Complexation Physiological Anesthetic
effect==== Menthol (mint)
Slide 90
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Raspberry Concentrate Imitation Vanillin0.180 g
Indol0.004 g Aldehyde C160.240 mL Diacetyl0.060 mL Phenylethyl
alcohol240 mL Aldehyde C140.015 mL Aldehyde C180.015 mL Aldehyde
C200.400 mL
Slide 91
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Raspberry Concentrate Imitation (contd) Orange flower
oil0.005 mL Ethyl butyrate0.120 mL Benzyl acetate0.075 mL Alpha
novoviol0.400 mL Beta novoviol0.200 mL Lemon oil0.060 mL Propylene
glycol qs100 mL
Slide 92
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Flavor Selection Guide SaltyButterscotch/Maple
BitterWild Cherry/Licorice Chocolate Mint Acrid/SourRaspberry/Fruit
Berry/Acacia Syrup
Slide 93
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Flavor Selection Guide (contd) OilyPeppermint/Anise
Wintergreen SweetFruit/Berry/Vanilla AcidCitrus
Slide 94
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Sweetening Pharmaceuticals Complex area Natural vs.
synthetic Heat stability
Slide 95
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Sweetening Agents Dextrose Mannitol Saccharin
Sorbitol Sucrose
Slide 96
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Coloring Pharmaceuticals Lighter shades
preferred
Slide 97
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Coloring Agents Dyes: FD&C, D&C, Ext D&C
Lakes: Calcium and aluminum salts Liquids: 0.001% to 0.0005%
Powders: 0.1% Caramel Ferric oxide: Red/yellow
Slide 98
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Coloring Agents (contd) Red No. 1,Ponceau 3R,Cherry
Red 9.8/5 Blue No. 1, Brilliant Blue, Blue-Green 20/20 Yellow No.
5, Tartrazine, Lemon Yellow 20/18
Slide 99
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Preservatives Sterilization and Preservation
Preservative Selection General Preservative Considerations Mode of
Action Preservative Utilization
Slide 100
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Sterilization and Preservation Some products must be
sterile Injectables Ophthalmics Sterilization Autoclave Filtration
Dry heat Irradiation
Slide 101
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Preservative Selection Dosage form Route of
administration Compatibility with excipients Container and closure
compatibility
Slide 102
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins General Preservative Considerations Range of activity
Concentration required pH requirements Compatibility
Slide 103
Copyright 2011 Wolters Kluwer Health | Lippincott Williams
& Wilkins Mode of Action Modification of cell membrane
permeability Lysis and cytoplasmic leakage Irreversible coagulation
of cytoplasmic constituents Inhibition of cellular metabolism
Oxidation of cellular constituents Hydrolysis
