RESUMEN
Introduction and 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 H1, 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 and Methods: various formulations including W/O and O/W 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 [lamda]max =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 gel. 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 Higuchis kinetic model