Topical Preparation Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department of Pharmaceutics Faculty of Pharmacy Omer Al-Mukhtar University Tobruk, Libya /05/251 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya

CONTENTS 1.Structure and function of the skin. 2.Factors affecting percutaneous absorption. 3.Drug-vehicle-skin interaction. 4.Dermatological formulations. 5.Liquid topical preparations. 6.Semi-solid topical preparations. 7.Bases used for topical preparations. 8.Release of drugs from ointments, creams and thermodynamics of their diffusion. 9.References. 2014/05/252 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya

Structure of the skin Epidermis:  Stratum corneum (Horny cell layer)  Stratum lucidum (Clear layer)  Stratum granulosum ( Granular Layer)  Stratum spinosum (Prickly layer)  Stratum germinativum Dermis: Hypodermis or Subcutaneous layer: 2014/05/253 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya

The human skin comprises three tissue layers: the stratified, avascular, cellular epidermis, the underlying dermis of connective tissue and subcutaneous fat. Hairy skin contains hair follicles and sebaceous glands; the glabrous skin of the soles and palms produces a thick epidermis with a compact stratum corneum, but there are no hair follicles or sebaceous glands. 2014/05/25 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya 4 Structure of the skin

2014/05/25 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya 5 Structure of the skin

2014/05/25 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya 6 Structure of the skin

2014/05/25 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya 7 Structure of the skin

Functions of the Skin The skin performs many varied functions but here we need consider only some aspects of its containment and protective roles. 1.Mechanical function 2.Protective function a.Microbiological barrier b.Chemical barrier c.Radiation barrier d.Heat barrier and temperature regulation e.Electrical barrier f.Mechanical shock 2014/05/25 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya 8

Factors affecting percutaneous absorption  Physico chemical properties of parent molecule  Solubility and partition co- efficient  pH condition  Penetrant concentration  Physico chemical properties of drug delivery system  Release characteristic  Composition of drug delivery system  Permeation enhancer used 2014/05/259 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya

 Physiological and pathological condition of skin  Lipid film  Skin hydration  Skin temperature  Effect of vehicle  Pathological injury to skin  Biological factors  Skin age  Thickness of S. Corneum  Skin condition 2014/05/25 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya 10 Factors affecting percutaneous absorption

 Chronic use of certain drugs  Presence of hair follicles  Blood flow  Regional skin sites  Species difference 2014/05/25 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya 11 Factors affecting percutaneous absorption

Drug-vehicle-skin interaction Patients also tend to favour creams rather than gels or ointments. Select a vehicle that promotes healing and does no further damage, as it to apply a therapeutic agent. Most vehicles are blended from one or more of three main components-aqueous solvents, powder and oil- together with thickening and emulsifying agents, buffers, antioxidants, preservatis, colours, propelants etc. 2014/05/2512 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya

Dermatological formulations 1.Liquid preparations 2.Gels (jellies) 3.Powders 4.Ointments 5.Creams 6.Pastes 7.Aerosols 2014/05/2513 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya

Liquid topical preparations Liquid preparations for external application include simple soaks or baths, applications, liniments, lotions, paints, varnishes, tinctures, and ear drops. A simple soak provides an active ingredient in aqueous solution or suspension, sometimes with water-miscible solvents. Gums and gelling agents may vary the consistency, from mobile liquids to stiff ringing gels. Bath additives such as Oilatum Emollient deposit a layer of liquid paraffin on the stratum corneum in an attempt to maintain its moisture content by occulsion. 2014/05/2514 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya

Semi-solid topical preparations Gels (jellies) are two-component semisolid systems rich in liquid. Their one characteristic feature is the presence of a continuous structure providing solid like properties. In a typical polar gel, a natural or synthetic polymer builds a three-dimensional matrix throughout a hydrophilic liquid. Ointments are greasy, semisolid preparations, often anhydrous and containing dissolved or dispersed medicaments. 2014/05/2515 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya

Bases used for topical preparations Hydrocarbon bases: These usually consist of soft paraffin or mixtures with hard paraffin. Fats and fixed-oil bases: Dermatological vehicles have frequently contained fixed oils of vegetable origin, consisting essentially of the mono-, di- and triglycerides of mixtures of saturated and unsaturated fatty acids. Silicones bases: Dimethicones, or dimethyl polysiloxanes, have properties similar to hydrocarbon bases. 2014/05/2516 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya

Absorption bases: Absorption bases soak up water to form water-in-oil emulsions while retaining their semisolid consistencies. Emulsifying bases: These essentially anhydrous bases contain oil-in-water emulsifying agents which make them miscible with water and so washable or ‘self-emulsifying’. Water-soluble bases: Formulators prepare water- soluble bases from mixtures of high and low molecular weight polyethylene glycols (macrogols, carbowaxes) 2014/05/25 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya 17 Bases used for topical preparations

Release of drugs from ointments, creams and thermodynamics of their diffusion Partitioning of the medicament between the emulsion phases. The addition of preservatives. Determination of a true viscosity for the diffusing molecules in the vehicle. The possibility of phase inversion or cracking of the emulsion when applied to the skin. Drug may also be trapped in the micelles and the gel and liquid crystalline phases present in the continuous phase. 2014/05/2518 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya

THANK YOU /05/2519 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya