Cream Formulation

Cream Formulation Contents  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

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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 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?

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 properties of 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  Discoloration  Precipitation

….visual..?

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 compounds 1. 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 excipients Nizoral 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