phm4153 cream formulation

Cream Formulation

Kausar AhmadKulliyyah of Pharmacy

http://staff.iiu.edu.my/akausar/PHM4153

http://staff.iiu.edu.my/akausar/PHM4153

PHM4153 Dosage Design 2 2009/10

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)

BindersFillersPreservatives etc.

to produce dosage formsOral (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 i


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

QExample?


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 formulationAnti-oxidants

Anti-bacterials

Preservatives

UV absorbers


Excipients in CREAMS

Bases….. SAA

Anionic - SDSNon-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

Encapsulation

Why?


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

Carrier for insoluble ingredientsProtector for sensitive ingredientsSlow delivery & long lasting effect

10 m, porous 7 m, empty spheres

20 m

Pore volume distribution of porous polyamide particles



Incompatibility

PhysicalImmiscibilit

y

insolubility

ChemicalpH 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)


Drug type and pH of medium

pHbasic

acidic

neutral

DrugPromethazine

Chlorhexidine

Ibuprofen

Fentiazac

Piroxicam

Fluorouracil

Crotamiton

Hydrocortisone acetate


Incompatibility

Formulation and packaging materials

E.g. softening of plastic containers by methyl

salicylate ointment.

Q What reaction occurs?


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 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


References

1. http://www.eastman.com/Markets/Pharmaceutical/Excipients/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/InsolubleKollidon.pdf

http://www.eastman.com/Markets/Pharmaceutical/Excipients/Excipients_intro.asp

http://www.eastman.com/Markets/Pharmaceutical/Excipients/Excipients_intro.asp

http://www.pharmaceutical-technology.com/contractors/materials/uniqema/

http://www.pharmaceutical-technology.com/contractors/materials/uniqema/

http://www.pformulate.com/

http://images.vertmarkets.com/CRLive/files/Downloads/89FB7970-7376-44A0-B6B6-4B171E4B978B/InsolubleKollidon.pdf



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