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Cream FormulationContents
Ideal formulation
Types of excipients
Functions
Factors for consideration
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.
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.
Excipients
Other components other than ACTIVE ingredient/s intentionally added to…….formulation
Ideal formulation
Non-irritant
Non-allergenic
Non-staining
Easy to apply
Pleasant feeling to the skin
Non-toxic
Non-harmful
Incapable of microorganism growth
Free from side-effects
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
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
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…..
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
Bases for Creams
Bases from mixtures of low and high MW PEG
Liposomes
Microemulsions
Multiple emulsions
Fluorocarbon emulsions – ultra low γ i
Functions of excipients
Aid processing during manufacturing
Protect, support, or enhance stability and bioavailability
Assist product identification à colour
Improve effectiveness and safety of product during storage or use
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
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.
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 absorbers
Excipients in CREAMS
Bases…..
SAA
Anionic - SDS
Non-ionic – Span, Tween
Anti-oxidants – BHA, BHT
Preservatives: methyl and propyl paraben (potency, integrity, prevent microbial growth)
Stearic acid
Stearyl alcohol, cetyl alcohol
Glycerol monostearate
Lanolin
Glycerin
Zinc stearate
opacifying agent, dusting powder…..
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
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…..
Delivery systems (in cosmetics)
Vesicular
liposomes & niosomes
Molecular
cyclodextrin
Particulate
Microcapsules, matrix particles
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
Effect of type of preparationAbsorption of retinyl palmitate
18% absorbed from acetone vehicle
compared to only
4% absorbed from o/w emulsion
Q What is the mechanism of absorption?
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
Types
Physical and chemical propertiesof excipients
solubility
hygroscopicity
swelling
hydration capacity
particle size distribution
bulk density, tap density
specific surface area
complexation
infrared spectrum
microbes
Polyamide – an excipient
20 µ m
Carrier for insoluble ingredients Protector for sensitive ingredients Slow delivery & long lasting effect
Incompatibility
Chemical
pH effects – dissociation?
pH and disperse systems
Soap emulsions and polyvalent cations
Complexation
Cationic and anionic compounds of high MW
Reducing agents (cause fading of dyes)
Physical
Immiscibility
insolubility
Drug type and pH of medium
Drug
Promethazine
Chlorhexidine
Ibuprofen
Fentiazac
Piroxicam
Fluorouracil
Crotamiton
Hydrocortisone acetate
pH
Basic
acidic
Neutral
Incompatibility
Formulation and packaging materials
E.g. softening of plastic containers by methyl salicylate ointment.
Detection of Incompatibility
Cracked cream
Hydrolysis or oxidation ….visual..?
Discoloration
Precipitation
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.
Cationic compounds1. Tertiary ammonium compounds
Cetrimide
Cetylpyridinium chloride
Benzalkonium salts
Domiphen bromide
2. Chlorhexidine salts
3. Dequalinium salts
4. Acridines
5. Triphenylmethane dyes
6. Neomycin sulphate
Exercise: Determine functions of excipientsNizoral cream
Ketoconazole
PPG
Steary alcohol
Cetyl alcohol
Sorbitan stearate
Polysorbate
Isopropyl myristate
Sodium sulfite
Purified water
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 - pH