فرمولاسيون فرآورده موضعي دوكسپين موثر در درمان اگزماي آتوپيك و ارزيابي جذب پوستي دارو در پوست جداشده موش صحرايي

Topical Formulation of Doxepin and Ex vivo Evaluation of Drug Percutaneous Absorption in Atopic Dermatitis

Introduction & Objective: Atopic dermatitis (AD) is a chronic and inflammatory skin disorder characterized by erythematous, eczematous, and highly pruritic lesions. Topical corticosteroids and oral antihistamines such as hydroxyzine, diphenhydramine, and promethazine are useful for the control of pruritus. Doxepin, a tricyclic antidepressant, with potent H=, H2 and muscarinic receptor blocking activity has recently been licensed as a topical treatment (Zonalon® 5% cream) by the Food and Drug Administration (FDA) for the short term (up to 8 days) management of moderate pruritus in adults with atopic dermatitis and lichen simplex chronicus. The objective of this investigation was to evaluate the physicochemical stability of various dermatological preparations of doxepin. Furthermore, the Ex-vivo percutaneous absorption of drug profiles obtained from different formulations was compared. Materials & Methods: Various formulations including MO and OM emulsions, and jelly base were prepared and the in vitro release and penetration characteristics of doxepin from each preparation were studied through a hydrophilic Dora pore diffusion barrier and membrane excised rat skin using Franz cell over a period of 6h. The amount of drug released from topical preparations were determined spectrophotometrically at Amax =292 nm. Results: The obtained results showed that the prepared formulations presented both good chemical and physical stabilities. The generated rank order for the drug release from different preparations using membrane was observed to be doxepin cream 5%> doxepin get. The Ex vivo penetration of doxepin through excised rat skin showed that the cumulative percent of penetrated drug at the end of each experiment were 75.5 % and 44.2 % for doxepin cream and doxepin gel respectively. Conclusion: The in vitro release kinetic of doxepin is not affected by the kind of topical dosage form (gel or cream). The release of drug from both cream and gel formulations obeyed Higuchiʹs kinetic model.