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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.

Cream Formulation

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Page 1: Cream Formulation

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.

Page 2: Cream Formulation

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

Page 3: Cream 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

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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…..

Page 5: Cream Formulation

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

Page 6: Cream Formulation

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.

Page 7: Cream Formulation

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

Page 8: Cream Formulation

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…..

Page 9: Cream Formulation

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

Page 10: Cream Formulation

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

Page 11: Cream Formulation

Types

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Physical and chemical propertiesof excipients

solubility

hygroscopicity

swelling

hydration capacity

particle size distribution

bulk density, tap density

specific surface area

complexation

infrared spectrum

microbes

Page 15: Cream Formulation

Polyamide – an excipient

20 µ m

Carrier for insoluble ingredients Protector for sensitive ingredients Slow delivery & long lasting effect

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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

Page 18: Cream Formulation

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

Page 19: Cream Formulation

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

Page 20: Cream Formulation

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

Page 21: Cream Formulation

Purified water

Phosphoric acid - pH