Cream Formulation

Kausar Ahmad
Kulliyyah of Pharmacy

http://staff.iiu.edu.my/akausar/PHM4153
 Contents
 Ideal formulation
 Types of excipients
 Functions
 Factors for consideration

PHM4153 Dosage Design 2 2009/10

Every medicinal product is a combination of the
drug substance and excipients.

Knowledge of the composition, function, and

behavior of excipients is a prerequisite to the
successful design, development and
manufacture of pharmaceutical dosage forms.

PHM4153 Dosage Design 2 2009/10

 Formulation
 Process whereby drugs are combined with other
substances (excipients)
 Binders
 Fillers
 Preservatives etc.
 to produce dosage forms
 Oral (liquid, solid)
 Parenteral (IV, aqueous or oily injections)
 Rectal (suppositories, aerosols)
 Topical (cream, ointment, lotion)

 suitable for administration to or by patients.

PHM4153 Dosage Design 2 2009/10
 Excipients
 Other components other than ACTIVE
ingredient/s intentionally added
to…….formulation

PHM4153 Dosage Design 2 2009/10

 Ideal formulation

 Non-irritant
Non-toxic

 Non-allergenic
Non-harmful

 Non-staining
Incapable of microorganism growth

 Easy to apply
Free from side-effects
 Pleasant feeling to
the skin
PHM4153 Dosage Design 2 2009/10
 Requirement of formulation
efficacy, safety, and quality

 Contain an accurate dose

 Be convenient to take or administer
 Provide the drug in a form for absorption or other
delivery to the target
 Retain quality throughout the shelf life and usage
period
 Be manufactured by a process that does not
compromise performance and that is reproducible and
economical

PHM4153 Dosage Design 2 2009/10

Factors to be considered in formulation

 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
PHM4153 Dosage Design 2 2009/10
 Physicochemical Properties
 Oils susceptible to oxidation
 Incorporate antioxidants
 E.g. BHT, BHA

 Aqueous solutions support microbial growth

 Incorporate water-soluble preservatives
 E.g. methyl and propyl paraben
 BUT these may affect the endocrine…..

PHM4153 Dosage Design 2 2009/10

 Examples of Creams
 Whitening
 Benzophenone, Hydroquinone
 Herbal-based (fair & lovely)
 Pearl
 Fruit extracts (olay, estee)
 Anti-ageing
 Collagen, seaweed extract (Imedeen)
 liposome
 Virility
 Active: fish & herbs (2 types)
 Excipients: aromatic emollient, Vitamin E, D-
panthenol
PHM4153 Dosage Design 2 2009/10
 Bases for Creams
 Bases from mixtures of low and high
MW PEG
 Liposomes
 Microemulsions
 Multiple emulsions
 Fluorocarbon emulsions – ultra low i

PHM4153 Dosage Design 2 2009/10

 Functions of excipients
 Aid processing during manufacturing
 Protect, support, or enhance stability and
bioavailability
 Assist product identification  colour
 Improve effectiveness and safety of product
during storage or use
Q Example?
PHM4153 Dosage Design 2 2009/10
 Choice of 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

PHM4153 Dosage Design 2 2009/10

 Limitation in choice of excipients
 no single excipient would satisfy all the criteria;
therefore, a compromise of the different
requirements has to be made.
 For example, although widely used in pharmaceutical tablet
and capsule formulations as a diluent, lactose may not be
suitable for patients who lack the intestinal enzyme lactase
to break down the sugar, thus leading to the gastrointestinal
tract symptoms such as cramps and diarrhea.
PHM4153 Dosage Design 2 2009/10
 Categories of excipients
 Provide essential parts of dosage form
 Emulsifiers

 Suspending agents
 Gelling agents
 Binders

 Prevent degradation of the formulation

 Anti-oxidants

 Anti-bacterials

 Preservatives

 UV absorbersPHM4153 Dosage Design 2 2009/10

 Excipients in CREAMS
 Bases…..  Stearic acid
 SAA  Stearyl alcohol, cetyl
 Anionic - SDS alcohol
 Non-ionic – Span,  Glycerol monostearate
Tween  Lanolin
 Anti-oxidants – BHA, BHT  Glycerin
 Preservatives: methyl and  Zinc stearate
propyl paraben (potency,
integrity, prevent  opacifying agent,
microbial growth)
dusting powder…..
PHM4153 Dosage Design 2 2009/10
Microstructural properties of creams
 texture and consistency is determined by the phase
behaviour of the component emulsifiers.
 Rheological, thermal and microscopical means
characterise the physico-chemical properties
 X-ray diffraction data

PHM4153 Dosage Design 2 2009/10

Effect of carrier on drug delivery
 Must not interact with active substance
 Control rate of release from vehicle…
 What are the delivery systems?
 Alter stratum corneum resistance……
 Physical? Chemical?
 Enhance stratum corneum hydration…..

PHM4153 Dosage Design 2 2009/10

Delivery systems (in cosmetics)
 Vesicular
 liposomes & niosomes
 Molecular Encapsulatio
n
 cyclodextrin
Why?
 Particulate
 Microcapsules, matrix
particles
PHM4153 Dosage Design 2 2009/10
 Excipients as
Penetration enhancers
Increase delivery of active substance
1. Disturb packing of SC lipid bilayers…..
 Examples: Sulfoxides, alcohols, polyols, alkanes, esters,
amines/amides of fatty acids, terpenes, surfactants,
cyclodextrins

2. disruption of skin barrier

 Extraction of skin lipids with apolar solvents e.g. acetone
 Physical stripping
 Physically or chemically induced irritation
PHM4153 Dosage Design 2 2009/10
Effect of type of preparation
Absorption of retinyl palmitate

18% absorbed from acetone vehicle

compared to only
4% absorbed from o/w emulsion

Q What is the mechanism of absorption?

PHM4153 Dosage Design 2 2009/10

 Excipients for hydration

 Hygroscopic effect of NaCl, sorbitol,

polypropylene glycol, glycerol
 Low MW glycerols alter water-binding capacity
of corneocytes
 Urea not for < 5 years old
Gives moisturising effect

PHM4153 Dosage Design 2 2009/10

Types

PHM4153 Dosage Design 2 2009/10

PHM4153 Dosage Design 2 2009/10
Physical and chemical properties
of excipients
 solubility
bulk density, tap density
 hygroscopicity
specific surface area
 swelling
complexation
 hydrationspectrum
infrared capacity
 particle size distribution
microbes

PHM4153 Dosage Design 2 2009/10

 Polyamide – an excipient
10 m, porous 7 m, empty spheres

20 m Carrier for insoluble ingredients

Protector for sensitive ingredients
Slow delivery & long lasting effect

PHM4153 Dosage Design 2 2009/10

Pore volume distribution
of porous polyamide
particles

PHM4153 Dosage Design 2 2009/10

 Incompatibility
 Chemical
 pH effects – dissociation?
 pH and disperse systems
 Physical
 Soap emulsions and polyvalent
 Immiscibilit
cations
y
 Complexation
 insolubility
 Cationic and anionic
compounds of high MW
 Reducing agents (cause fading
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Drug type and pH of medium

Drug
Promethazine
Chlorhexidine pH
Ibuprofen basic
Fentiazac acidic
Piroxicam neutral
Fluorouracil
Crotamiton
Hydrocortisone acetate

PHM4153 Dosage Design 2 2009/10

 Incompatibility
 Formulation and packaging materials
 E.g. softening of plastic containers by methyl
salicylate ointment.

Q What reaction occurs?

PHM4153 Dosage Design 2 2009/10

 Detection of Incompatibility
 Cracked cream
 Hydrolysis or oxidation ….visual..?
 Discoloration
 Precipitation

PHM4153 Dosage Design 2 2009/10

 Emulsifying Wax BP
 Incorporation of anionic emulgent resulted
in the following:
 Crack
 Hinder release of cationic medicaments
 Lower the antimicrobial activity of a cationic
medicament or preservative.

PHM4153 Dosage Design 2 2009/10

 Cationic compounds
1. Chlorhexidine
2. Tertiary ammonium
salts compounds
 Cetrimide
3. Dequalinium salts
 Cetylpyridinium chloride
4. Acridines
Benzalkonium salts
5. Triphenylmethane
Domiphen bromide dyes

6. Neomycin sulphate

PHM4153 Dosage Design 2 2009/10

 Exercise:
Determine functions of excipients
Nizoralcream
Elomet cream 0.1%
 Mometasone
 Ketoconazolefuroate
 White
 PPG petrolatum
 White
 Stearywax
alcohol
 PPG
 Cetyl stearate
alcohol
 Stearyl
 Sorbitanalcohol
stearate
 Ceteareth-20
 Polysorbate
 Hexylene
 glycol
Isopropyl myristate
 Titanium
 dioxide
Sodium sulfite
 Al
 starchwater
Purified octenylsuccinate
 Purified water
 Phosphoric acid - pH

PHM4153 Dosage Design 2 2009/10

 References
1. http://www.eastman.com/Markets/Pharmaceutical/Excip
ients/Excipients_intro.asp
2. http://www.pharmaceutical-technology.com/contractors/
materials/uniqema/
3. http://www.pformulate.com/
4. http://images.vertmarkets.com/CRLive/files/Downloads/
89FB7970-7376-44A0-B6B6-4B171E4B978B/Insoluble
Kollidon.pdf

PHM4153 Dosage Design 2 2009/10