KAUSAR AHMAD KULLIYYAH OF PHARMACY Cream Formulation 1 PHM4153 Dosage Design 2 2011/12.
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Transcript of 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
Contents
PHM4153 Dosage Design 2 2011/12
Ideal formulatio
n
Types of excipients Properties
2
Examples of Creams
PHM4153 Dosage Design 2 2011/12
• Benzophenone, hydroquinone
• Fruit extracts
Whitening
• Collagen, seaweed extract • Liposome
Anti-ageing
• Fish• Herbs Virility
3
Formulation
PHM4153 Dosage Design 2 2011/12
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.
4
Ideal formulation
PHM4153 Dosage Design 2 2011/12
5
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
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
6
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
7
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
8
Examples of Oils & Fats
PHM4153 Dosage Design 2 2011/12
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• Cyclomethicones• DimethiconesSilicones
• Castor oil• Glyceryl tricaprylate
Triglycerides/ vege oils
• Octyl stearate• Isopropyl palmitate
Simple esters
Advantages of Silicones
PHM4153 Dosage Design 2 2011/12
10
Chemical and physical• stable, colourless, odourless
Cosmetic• Skin-feel, gloss/matte
Dermo-toxicology• Not sensitizing, non-comedogenic,
Examples of Lipids
PHM4153 Dosage Design 2 2011/12
11
• Mineral oilHydrocarbons
• BeeswaxWax
• Dicaprilyl etherEther
• Cetyl alcoholAlcohols
• Stearic acidAcids
Properties Limitation
PHM4153 Dosage Design 2 2011/12
Emollient effectShineLubricitySpreadabilitySolvencyDrying
OdourColourViscosityMiscibility with
other oilsToxicityImpuritiesCost
12
Choosing Oils
Non-polar Polar
PHM4153 Dosage Design 2 2011/12
Lasting emollient effect
Barrier effectInertStable against
oxidationShineSpreadabilitycheap
Varying emollient effect
Little barrier effectVarying stability
against oxidationGood absorptionGood deliveryexpensive
13
Polarity of oils
Excipients
PHM4153 Dosage Design 2 2011/12
Other components other than API added to formulation
14
Categories of excipients
PHM4153 Dosage Design 2 2011/12
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
15
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
16
Emulsifiers
PHM4153 Dosage Design 2 2011/12
17
w/o
o/w
Penetration enhancers
PHM4153 Dosage Design 2 2011/12
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
18
Increase delivery of active substance by:
Hydration
PHM4153 Dosage Design 2 2011/12
Hygroscopic effect
NaCl Sorbitol
PPG glycerol
Alter water-binding capacity of corneocytes
Low MW glycerol
s
19
Q. How does urea moisturise the skin?
PHM4153 Dosage Design 2 2011/12
20
PHM4153 Dosage Design 2 2011/12
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pH adjustment
PHM4153 Dosage Design 2 2011/12
22
Triethanolamine
NaoH
Preservatives
PHM4153 Dosage Design 2 2011/12
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Sodium methyl/butyl/propyl paraben
Imidazolidinyl urea
Anti-oxidant
PHM4153 Dosage Design 2 2011/12
24
Butyl hydroxy tolueneButyl hydroxy anisole
UV filters
PHM4153 Dosage Design 2 2011/12
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Zinc oxide
Titanium dioxide
Benzophenone
Other types of excipients
PHM4153 Dosage Design 2 2011/12
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Soothing•Allantoin
Anti-free radicals•Polyphenols
Effects of excipients
PHM4153 Dosage Design 2 2011/12
texture and consistency
phase behaviour of the component
emulsifiers.
physicochemical properties
rheological, thermal and
microscopical
27
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…..
28
Physical and chemical properties of excipients
PHM4153 Dosage Design 2 2011/12
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solubility hygroscopicity swelling hydration
capacity
particle size distribution
bulk & tap density
specific surface area
complexation
infrared spectrum microbes
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
Excipient: Particle size distribution
PHM4153 Dosage Design 2 2011/12
31
Excipient: Pore volume & pore diameter
PHM4153 Dosage Design 2 2011/12
32
Incompatibility
PHM4153 Dosage Design 2 2011/12
33
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
PHM4153 Dosage Design 2 2011/12
Cracked cream
Hydrolysis or
oxidation
Discoloration
Precipitation
34
Effect of type of preparation: Absorption of retinyl palmitate
PHM4153 Dosage Design 2 2011/12
Exercise:
18% absorbed from acetone vehicle
compared to only
4% absorbed from o/w emulsion
Q WHY?
35
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
36
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
37
PHM4153 Dosage Design 2 2011/12
38
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.