Topical Semi Solid Dosage Forms - II

Topical creams

Semisolid preparations containing one or more medicinal agents dissolved or dispersed in either a water in oil emulsion or an oil in water emulsion or in another type of water washable base.

Opaque, non-greasy, viscous to mildly greasy

Generally contain <50% hydrocarbons or PEGs as the vehicle and or >20% water/volatiles

Tend to mostly evaporation or be absorbed when applied to skin

Creams may be preferred to ointments

Topical cream bases

W/O emulsion (cold cream)

O/W emulsion or vanishing cream with high concentration of water

High-shear homogenization employed to reduce particle or droplet size and improve the physical stability of the resultant dosage form

Preservatives usually added if cream not going to be used right away

Composition of the O/W cream

Oil phase: stearic acid, stearyl alcohol, cetyl alcohol

Aqueous phase: glycerin, methylparaben, KOH, water

Procedure of O/W creams

Heat oil phase then heat water phase

Add oil phase slowly to water phase while stirring

Cool and homogenize

Cool with mixing

Ointments vs creams - Ointments

Usually translucent

oil base (<20% water)

More greasy

Thick and more viscous

less water washable

less spreadable, make an occlusive layer on the skin

Absorbed more slowly by the skin, slower onset of action

May interfere with skin functions

may not need preservatives

Ointments vs creams - creams

White or off white incolor

Water based >20% water

less/non greasy

thin and less viscous

waster washable

Easily spreadable, suitable for large surface area

Absorbed faster by the skin

Faster onset of action

interfere less with skin functions

Preservatives are usually required

Topical lotions

Opaque and non-greasy, lower viscosity than creams

Generally, contain a water-based vehicle >50% water/volatiles

most commonly O/W

Dries quickly on skin

Topical gels

Three-dimensional physical or chemical cross-linked matrix with a gelling agent added. Provide a cooling sensation when applied to the skin.

Not greasy

often shear thinning

Preparation of topical gels

Formed by crosslinking macromolecules dispersed in the continuous phase. Crosslinking and changing pH via carbomers. Vigorous mixing or milling or shaking recommended for uniformity

Store in tight containers to prevent water loss

Avoid freezing

Pastes

Contain a large portion (20-50%) solids. Finely dispersed in an aqueous or fatty vehicle. Highly viscous, stiff, adherent formulations for the application and retention of medication in a local area.

Opaque, greasy to mildly greasy

Stiffer than ointments

Adhere well to skin, water impermeable, prevent dehydration

Paste preparation

Same as ointments by cold incorporation or fusion. If a levigating agent is to be used, a portion of the base is used instead of a liquid for softening the paste

Decision tree

1. Does this product have sufficient quantities of gelling agent to form a 3D matrix? Yes then gel.

2. Does it contain a large portion (20-50%) of dispersed solids? Yes then paste

3. Does it contain >20% volatiles? Yes then go to 4a. No Test 4b.

4a:

1. Is it pourable liquid with a viscosity <30,000 centipoise? Yes then lotion, no then cream

4b:

1. Does it contain >50% hydrocarbons or PEG as the vehicle and <20% of volatiles? Yes then ointment, no then cream.

Stability of semisolids

Most are intrinsically unstable (thermodynamically). Their rate of change is slow, they are kinetically stable. Emulsions can break and separate. Crystallization can also occur changing consistency.

Oxidation of components is common with natural oils and waxes

Los of volatile components (water, fragrance)

Accelerated stability testing is a problem for semi soids

USP requirements for topical semisolids

Drug must retain potency / purity

Appearance and elegance - look good feel good?

Uniformity - no physical separation during manufacturing/storing

Particle size - distribution, aggregation of API

Rheological behavior (non Newtonian)

Water activity

In vitro permeation testing and release testing

Performance criteria

Quality attributes:

• Physical and chemical stability

• Free from contamination

• Elegance

• Bioavailability

Quality attributes must be maintained over the labeled shelf life under recommended storage conditions and must be reproducible from batch to batch and from one dose to another in the same batch

Packaging of semisolids

Jars, tubes or syringes

Jars made of clear or opaque glass/plastic

Tubes are made of aluminum or plastic

Jars filled by transferring weighed amount of product into the jar with a spatula avoiding entrapment of air. Product should not be so high as to touch the lid when closed.

Tubes are filled from the open back then heat sealed