Transcript Formulation of Cream and Ointment

Cream Formulation
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KAUSAR AHMAD
KULLIYYAH OF PHARMACY
http://staff.iium.edu.my/akausar
PHM4153 Dosage Design 2 2011/12
Contents
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Ideal
formulation
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Types of
excipients
Properties
Examples of Creams
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Whitening
• Benzophenone, hydroquinone
• Fruit extracts
Antiageing
• Collagen, seaweed extract
• Liposome
Virility
• Fish
• Herbs
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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-harmful
Incapable of
microorganism
growth
Free from sideeffects
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Formulation requirement: efficacy, safety, and quality
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Contain accurate
dose
Convenient to
take or
administer
Retain quality
throughout shelf
life & usage period
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Provide drug in a
form for
absorption or
other delivery to
the target
Manufactured by a
process that does not
compromise
performance and that is
reproducible and
economical
Factors to be considered in formulation
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Physicochemical properties
Choice of vehicle
• Waxes and oils or emulsions
Categories of excipients
• Provide essential part of the dosage form
• Prevent degradation of the formulation
Stability
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Choice of vehicle
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Bases from
mixtures of low
and high MW
PEG
Liposomes
Multiple
emulsions
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Microemulsions
Fluorocarbon
emulsions –
ultra low i
Examples of Oils & Fats
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Silicones
• Cyclomethicones
• Dimethicones
Triglycerides/
vege oils
• Castor oil
• Glyceryl tricaprylate
Simple esters
• Octyl stearate
• Isopropyl palmitate
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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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Hydrocarbons
• Mineral oil
Wax
• Beeswax
Ether
• Dicaprilyl ether
Alcohols
Acids
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• Cetyl alcohol
• Stearic acid
Choosing Oils
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Properties
Limitation
 Emollient effect
 Odour
 Shine
 Colour
 Lubricity
 Spreadability
 Solvency
 Drying
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 Viscosity
 Miscibility with other
oils
 Toxicity
 Impurities
 Cost
Polarity of oils
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Non-polar
Polar
 Lasting emollient effect
 Varying emollient
 Barrier effect
 Inert

 Stable against

oxidation
 Shine
 Spreadability
 cheap
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


effect
Little barrier effect
Varying stability
against oxidation
Good absorption
Good delivery
expensive
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
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physiological
inertness
commercially
available at
low cost
physical and
chemical
stability
absence of
pathogenic
microbial
organisms
conformance
to regulatory
agency
requirements
no interference
with drug
bioavailability
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Emulsifiers
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w/o
o/w
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Penetration enhancers
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Increase delivery of active substance by:
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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Hydration
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Hygroscopic effect
NaCl
Sorbitol
PPG
glycerol
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Alter water-binding
capacity of
corneocytes
Low MW
glycerols
Q. How does urea moisturise the skin?
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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 toluene
Butyl 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
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texture and consistency
phase behaviour of
the component
emulsifiers.
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physicochemical
properties
rheological, thermal
and microscopical
Physicochemical properties
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Oils susceptible to
oxidation
Add antioxidants
• E.g. BHT, BHA
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Aqueous solutions support
microbial growth
Add preservatives
• E.g. methyl and
propyl paraben
• BUT these may
affect the
endocrine…..
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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Polyamide: Carrier for insoluble ingredients; Protector for
sensitive ingredients; Slow delivery & long lasting effect
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7 m, empty spheres
10 m, porous
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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
Physical
pH/dissociation
Immiscibility
pH/disperse
systems
Insolubility
polyvalent cations
complexation
cationic and anionic
compounds of high MW
reducing agents (cause
fading of dyes)
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Packaging
Formulation and
packaging materials
Detection of Incompatibility
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Cracked
cream
Hydrolysis or
oxidation
Discoloration
Precipitation
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
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Nizoral cream
 Ketoconazole
 PPG
 Stearyl alcohol
 Cetyl alcohol
 Sorbitan stearate
 Polysorbate
 Isopropyl myristate
 Sodium sulfite
 Purified water
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Elomet cream 0.1%
 Mometasone furoate
 White petrolatum
 White wax
 PPG stearate
 Stearyl alcohol
 Ceteareth-20
 Hexylene glycol
 Titanium dioxide
 Al starch octenylsuccinate
 Purified water
 Phosphoric acid
References
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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/89FB7970-7376-44A0B6B6-4B171E4B978B/InsolubleKollidon.pdf
Thank you to contributors.
PHM4153 Dosage Design 2 2011/12