Semisolid Dosage Forms312 PHT

Objectives -To introduce the student to the structure, functions

and topical treatment of human skin -To deal with the principles of membrane diffusion,

skin transport and properties affecting transdermal delivery

-To identify dermatological vehicles and methods of preparation

-To identify new trends in semisolid dosageform

SEMISOLID PREPRATIONS

DEFINITION:Semisolid dosage forms are products of semisolid consistency and applied to skin or mucous membranes for therapeutic or protective action or cosmetic function.

IDEAL PROPERTIES OF SEMISOLIDDOSAGE FORMS

1.PHYSICAL PROPERTIES- :a) Smooth textureb) Elegant in appearancec) Non dehydratingd) Non grittye) Non greasy and non stainingf) Non hygroscopic

IDEAL PROPERTIES OF SEMISOLIDDOSAGE FORMS

2 .PHYSIOLOGICAL PROPERTIES :-a) Non irritatingb) Do not alter membrane / skin functioningc) Miscible with skin secretiond) Have low sensitization effect

3 .APPLICATION PROPERTIES- :a) Easily applicable with efficient drug releaseb) High aqueous washability

TYPES OF CONVENTIONAL SEMISOLIDDOSAGE FORMS

1 .OINTMENTS-: -They are soft hydrocarbon based semisolid

preparations, e.g. pertrolatum. -Since they are mostly of greasy nature so they stain

cloths, are generally poor solvent for most drugs, and usuallydecrease the drug delivery capabilities ofthe system.

TYPES OF CONVENTIONAL SEMISOLIDDOSAGE FORMS

2 .CREAMS- : -They are viscous semisolid emulsion system with

opaque appearance compared with the translucentointments. Consistency and rheological charactersdepend on weather the cream is w/o or o/w.

-Properly designed O/W creams are elegant drug delivery system, pleasing in both appearance and feel aftar pplication.

-O/W creams are non greasy and are rinsable.They are good for most topical purposes

TYPES OF CONVENTIONAL SEMISOLIDDOSAGE FORMS

3 .PASTES:- - Pastes are basically ointments into which a high

percentage of insoluble solid has been added.The extraordinary amount of particulate matterstiffens the system.

-Pastes make particularly good protective barrierwhen placed on the skin chemicals before theyever reach the skin.

-Like ointments, paste forms an unbrokenrelatively water – impermeable film. Unlikeointments, the film is opaque and therefore, aneffective sun block accordingly.

TYPES OF CONVENTIONAL SEMISOLIDDOSAGE FORMS

4 .GELS (JELLIES)-: -Gels are semisolid coherent system in which a

liquid phase is constrained within a polymeric matrix (consisting of natural or synthetic gum) having high degree of physical or chemical cross-linking.

-Gels are aqueous colloidal suspensions of the hydrated forms of insoluble medicament.

-Gels are transparent or translucent non-greasy semisolid gels.

-They are used for medication orlubrication.

TYPES OF CONVENTIONAL SEMISOLIDDOSAGE FORMS

5 .POULTICES-:It is soft, viscous, pasty preparation for external use. They are applied to skin while they are warm, after spreading on or between layers of cloth . Poultice must retain heat for a considerable time because they areintended to supply warmth to inflamed partsof body.

-Poultices act by increasing blood flow, relaxing tense muscles, soothing inflamed tissues, or drawing toxins from an infected area. Thus, they can be used to relieve the pain and inflammation associated with abscesses; e.g. Kaolin poultice (B.P.C.)

TYPES OF CONVENTIONAL SEMISOLIDDOSAGE FORMS

7 SEMISOLID FOAMS:- -Foams are system in which air or some other gas is

emulsified in liquid phase to the point of stiffening. -E.g. shaving creams, whipped creams, aerosolized

shaving creams.

-Conventional topical vehicles, such as ointments, creams or gels, predominantly exert their effect by releasing the drug onto the skin surface, and the drug molecules then diffuse through the skin layers.

-The extent and duration of diffusion depends onthe (1) physicochemical properties of the drug,

)2 (the type of base and (3) skin condition. -In general, the modification of drug absorption

kinetics by these vehicles is the result of theirability to provide increased hydration byocclusion or some other mechanism.

Topical preparations

-Preparations for dermal use -Preparations for transdermal use

)percutaneous absorption(

Dermal and transdermal drug delivery

-Semisolid dosage forms for dermatological drugtherapy are intended to produce desired therapeuticaction at specific sites in the epidermal tissue.

-A drug’s ability to penetrate the skin’s epidermis,dermis, and subcutaneous fat layers will lead totransdermal (percutaneous) drug delivery giving riseto systemic action.

-Therefore, the extent the drug can travel through thedifferent skin layers determine the delivery system.

Why Transdermal drug delivery?

-Avoiding hepatic first pass effect -Continuous drug delivery

-Fewer side effect -Therapy can be terminated at any time

-Improved patient compliancesDisadvantages:

-cosmetically non-appealing -may display erratic (irregular) absorption

The fraction of the drug that penetrate the skinvia any route depends on:

–The physicochemical nature of the drug, specially its size, solubility and partition coefficient

–The site and condition of the skin –The formulation

–How vehicle component temporarily change theproperties of the stratum corneum

Skin Permeability -Basic principle of diffusion through membranes

Fick’s Law of Diffusion DAK/ h) (C 1-C2)) = dQ /dt

dQ/dt - rate of diffusion D - diffusion coefficient

A - surface area of membraneK - partition coefficienth - membrane thicknessC1 - C2 = concentration difference for soluteGenerally, C1>>C2

Skin PermeabilitySince D, K, and h are constant for a givendrug/membrane; and given that C1>>C2:

dQ / dt = PC1Where P - permeability constant

Ideal molecular properties for drugPenetration

-A low molecular weight (generally less than 500Daltons(

-An adequate solubility in oil and water -A balanced partition coefficient

-A low melting point -Potent drug (maximum 50 mg/day)

Factors Affecting TransdermalDelivery

-Physiological factors -Physicochemical factors

PHYSIOLOGICAL FACTORS1 .Skin condition –Intact skin is a barrier

–Damaged skin more permeable –Diseased skin usually more permeable

2 .Skin age -babies and children – greater area/weight than

adult- absorb more drug e.g. steroids -premature infants- no stratum corneum

-e.g. the use of topical caffeine for breathingdifficulties

PHYSIOLOGICAL FACTORS3 .Skin hydration

-important as it usually promotes permeation-principle factor

- -Rank order (decreasing): - occlusive film

- ointment - cream

4 .Regional skin site -wide variation, e.g. face to foot

PHYSICOCHEMICAL FACTORS1 .Temperature and pH

-diffusion depends on temperature(direct relationship). -nonionic molecules is more permeable than ionic

-Stratum corneum, pH = 4.5 – 6

-How pH affect drug penetration? ???

PHYSICOCHEMICAL FACTORS2 .Drug concentration

obeys Fick’s lawdQ/dt = KDC/h

3 .Partition coefficient -also obeys Fick’s law

-moderate value (Why????)4 .Diffusion coefficient

5 .Molecular size -absorption should be inversely proportion to size

)M.Wt(.

Topical dosage forms -Ointments

-Creams -Pastes

-Gels/jellies -Solution -Plasters -Aerosols -Powders

OintmentsAn ointment is a viscous semisolid preparation usedtopically on a variety of body surfaces. These includethe skin and the mucus membranes of the eye (an eyeointment), vagina, anus, and nose.An ointment may or may not be medicated.Typically used as:

Emollients to make skin more pliableProtective barriersVehicles in which to incorporate medication

Ointment1.2 .Ointment Bases

-Semisolid bases do not only act as the carriers of themedicaments, but they also control the extent of absorption ofmedicaments incorporated therin.

-An ointment base should be compatible with skin, stable,smooth, non-irritating, non-sensitizing, inert, capable ofabsorbing water or other liquid preparations, and of releasing

the incorporated medicament, readily. -A base for ophthalmic semisolids must be non-irritating to the

eye, and It should also be sterilizable conveniently.

Appropriate Selection of Ointment Base:Selection of ointment base depends on the following:

1 .Desired release rate of the drug substance from theointment base.

2 .Rate and extent of topical or percutaneous drugabsorption.

3 .Desirability of occlusion of moisture from skin.4 .Stability of the drug in the ointment base.5 .Effect of drug on the consistency of base.

6 .Easy removal of base on washing.7 .Characteristic of the surface to which it is applied

Ointment Bases -Ointment bases may be classified in

severalways but the following classification based oncomposition is generally used which are asfollow,A) Oleaginous (hydrocarbon) base.B) Absorption base.C) Emulsion base.D) Water soluble base.

Ointment basesA) Oleaginous (hydrocarbon) bases- :

This is a purified mix of liquid, semi-solid or -solid hydrocarbons from petroleum

-Most of the early ointment bases used to be exclusively oleaginous in nature but nowadaysthe materials obtained from plant, animal, aswell as synthetic origin are employed asoleaginous ointment bases.

-Combinations of these materials can produce awide range of melting points and viscosities

Ointment basesA) Oleaginous (hydrocarbon) bases- :

These bases are: -Immiscible with water (they are difficult to wash off)

-Not absorbed by the skin, remain on the skin forprolonged period of time without “drying out”

-Absorb very little water from formulation or fromskin exudates.

-Inhibit water loss from the skin by forming a waterproof film (OCCLUSIVE DRESSING).

-Improving hydration, may encourage penetration ofthe medication through skin.Examples: Vaseline, hard paraffin, liquid paraffin,white ointmentUses: protectants, emollient, and vehicle for soliddrugs

Ointment basesB) Absorption (Emulsifiable) Bases :-

Absorption bases (also called emulsifiablebases) are mostly W/O type emulsions andhave capacity to absorb considerable quantitiesof water or aqueous solution without markedchanges in consistency.

Ointment basesAbsorption bases are:

-less occlusive than the hydrocarbon bases. -Incorporation of aqueous solution is possible.

-easier to spread. -good emollients

-They hydrate the stratum corneum. -Not easily removed from the skin with water

washing (external phase is oleaginous) -Uses: protectants, emollient, and vehicle for

aqueous solutions and solid drugs

Ointment bases (cont.)Absorption base (cont.)

-Lanolin, anhydrous lanolin, wool fat, woolwax (obtained from wool of sheep)

-This is a type of wax- like that can absorb about 50%of its weight of water and is used in ointments inwhich the proportion of aqueous fluid is too large forincorporation into a hydrocarbon base.

-Wool fat is a major constituent of Simple OintmentBP

-Other examples: hydrous lanolin, bees wax andcholesterol (they are added to some ointment bases toincrease their water-absorbing power(

Ointment bases (cont.))C (Emulsion Bases:

-They are either w/o or o/w -Hydrophilic Ointment USP

-Cold cream: W/O emulsions, emollient, cleansing, notwater washable, non occlusive, shiny appearance, notneed glycerin.

-Vanishing cream: O/W emulsion contains large % ofwater and humectant. An excess of stearic acid in theformula helps to form a thin film when the waterevaporates.

Ointment bases (cont.)Properties of Emulsion bases:

-Water-washable, easier to remove -Non/less greasy

-Can be diluted with waterNon/less occlusive

-Better cosmetic appearance -Better compliance; Patients prefer cream to an

ointment because the cream spreads more readily, -less greasy, evaporating water soothes the inflamed

tissue.Uses: Cleansing creams, emollients and vehicle forsolid and liquid drugs.

D) Water Soluble Bases :- -Water soluble and water washable

“greaseless,” -Because they soften with the addition of water,

large amounts of aqueous solutions are noteffectively incorporated into these bases.

Uses: drug vehicle

D) Water Soluble Bases (cont.)- :The water-soluble bases have the advantages ofbeing:

-Water soluble and washable -Non-greasy, non-staining

-Non/less occlusive -Lipid free

-Relatively inert -Does not support mold growth

-Little hydrolysis, stable-Disadvantages: May dehydrate skin and hinder

percutaneous absorption.

-Polyethylene glycol (so called macrogols orcarbowax) are mixtures of poly-condensationproducts of ethylene oxide and water and they aredescribed by their average molecular weights

)viscous liquids to waxy solids.(

-Different grades of cabowaxes are available whichare designated by a number roughly representingtheir average molecular weights e.g.- PEG 200,PEG 400, PEG1000, PEG1540, and PEG 6000

A general rule is that: -For wet lesions the patient should use an

aqueous dressing, -For dry skin a lipophilic base is best.

Selection of the appropriate base -Desired release rate of drug substance

-Desirability for topical or percutaneousabsorption

-Desirability of occlusion -Stability of drug in ointment

-Effect of drug on ointment base -Desire for easy removable

METHODS OF OINTMENT PREPARATION1 BY TRITURATION-:

In this finely subdivided insoluble medicaments areevenly distributed by grinding with a small amount ofthe base followed by dilution with graduallyincreasing amounts of the base .

2 BY FUSION-:When soft fats or waxes are to be incorporated withhard fats or waxes then of this to be melted to gethomogenous mixture with stirring.

-ingredients are melted together in descending order

of their melting points.3 BY OINTMENT MILLS-:

It is used for large scale production where triple roller mill is utilized which is faster than others.

Requirement for ointments -Microbial content: do not need to be

sterile, but must meet the FDArequirement of the test for absence ofbacteria such as S. areus and P.aeruginosa for dermatologicalproducts.

-Packaging, storage, labeling: (labelshould include the type of base used(

-Additional standards: viscosity, invitro release

CREAM -Semisolid preparations containing one or

more medicinal agents dissolved in eitheran o/w or w/o emulsion or in another typeof water-washable base.

-Typically of low viscosity, two phasesystem (w/o or o/w), compared toointment.

-Appears “creamy white” due to thescattering of light.

-Traditionally, it is the w/o cold creamCurrently and most commonly, it is the o/w -

emulsion.

Creams as drug delivery systems -Good patient acceptance

-Water evaporation concentrates drug on skinsurfaceExamples;

Vanishing cream: o/w with high % of water and stearicacid.Cold cream: (an emulsion for softening and cleansing theskin): w/o, white wax, spermaceti, almond oil, sodiumborate.

CREAMEMULSIFIER : -

Important in creams-Ideal properties of emulsifier includes,

a) Must reduce surface tension for properemulsification.b) Prevents coalescence.

c)Effective at low concentration

Thank you!!..