Development of New Topical Formulations of Diphenhydramine Hydrochloride: In Vitro Diffusion and In Vivo Preliminary Studies

The aim of this study was to evaluate the vehicle effect on in vitro diffusion of Diphenhydramine hydrochloride (DPH) from new five topical formulations: microemulsion (A), microemulsion+silica (B), Na Alginate emulgel (C), Carbopol cream (D) and hydroxyethylcellulose gel (E).Furthermore, the skin irritation potential and the formulation effect on skin reaction induced by histamine were investigated in vivo. The commercial cream of DPH (Allergan) was used as reference formulation.The diffusion rate values showed the rank order E > A > B > C > D > Control, and all prepared formulations are able to improve the diffusion of drug compared with commercial cream; among the tested formulations, the hydroxyethylcellulose gel and microemulsions appear to be the most efficient vehicles in promoting the release of DPH.After in vivo application, the formulations do not produce skin irritation and determine a reduction of the response induced by histamine suggesting that their potential use as alternative topical dosage forms for effective local antihistaminic therapy.