kausar ahmad kulliyyah of pharmacy cream formulation 1 phm4153 dosage design 2 2011/12
TRANSCRIPT
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KAUSAR AHMADKULLIYYAH OF PHARMACY
Cream Formulation
http://staff.iium.edu.my/akausar
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PHM4153 Dosage Design 2 2011/12
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Contents
PHM4153 Dosage Design 2 2011/12
Ideal formulatio
n
Types of excipients Properties
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Examples of Creams
PHM4153 Dosage Design 2 2011/12
• Benzophenone, hydroquinone
• Fruit extracts
Whitening
• Collagen, seaweed extract • Liposome
Anti-ageing
• Fish• Herbs Virility
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Formulation
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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
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Formulation requirement: efficacy, safety, and quality
PHM4153 Dosage Design 2 2011/12
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
PHM4153 Dosage Design 2 2011/12
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
PHM4153 Dosage Design 2 2011/12
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
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Advantages of Silicones
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Chemical and physical• stable, colourless, odourless
Cosmetic• Skin-feel, gloss/matte
Dermo-toxicology• Not sensitizing, non-comedogenic,
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Examples of Lipids
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• Mineral oilHydrocarbons
• BeeswaxWax
• Dicaprilyl etherEther
• Cetyl alcoholAlcohols
• Stearic acidAcids
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Properties Limitation
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Emollient effectShineLubricitySpreadabilitySolvencyDrying
OdourColourViscosityMiscibility with
other oilsToxicityImpuritiesCost
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Choosing Oils
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Non-polar Polar
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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
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Excipients
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Other components other than API added to formulation
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Categories of excipients
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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
PHM4153 Dosage Design 2 2011/12
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
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Penetration enhancers
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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:
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Hydration
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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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PHM4153 Dosage Design 2 2011/12
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pH adjustment
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Triethanolamine
NaoH
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Preservatives
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Sodium methyl/butyl/propyl paraben
Imidazolidinyl urea
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Anti-oxidant
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Butyl hydroxy tolueneButyl hydroxy anisole
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UV filters
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Zinc oxide
Titanium dioxide
Benzophenone
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Other types of excipients
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Soothing•Allantoin
Anti-free radicals•Polyphenols
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Effects of excipients
PHM4153 Dosage Design 2 2011/12
texture and consistency
phase behaviour of the component
emulsifiers.
physicochemical properties
rheological, thermal and
microscopical
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Physicochemical properties
PHM4153 Dosage Design 2 2011/12
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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PHM4153 Dosage Design 2 2011/12
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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
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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
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Detection of Incompatibility
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Cracked cream
Hydrolysis or
oxidation
Discoloration
Precipitation
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Effect of type of preparation: Absorption of retinyl palmitate
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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
PHM4153 Dosage Design 2 2011/12
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
PHM4153 Dosage Design 2 2011/12
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.