In vitro diffusion studies for the assessment & optimization of promethazine hydrochloride dermatological formulations.

摘要

Promethazine Hydrochloride, a phenothiazine derivative, has antihistamine (H1 receptor blocker) and anticholinergic properties. It is used clinically to prevent and control motion sickness, nausea, vomiting, and dizziness, to relieve or prevent allergic reactions, and to relax and sedate patients before and after surgery. Usually, promethazine is administered as a tablet and syrup and as a suppository. Topical and transdermal formulations. are not currently commercially available, however, sometimes, they are compounded by Pharmacists. This study was undertaken to develop and screen various topical formulations of promethazine with optimum release and permeation through the skin.;Various formulations containing 6.25%, 12.5% and 25% of drug were developed using cationic (Carbopol 934-P) gel base and nonionic (HPMCK100M) gel base. Also, the effects of penetration enhancers, dimethylsulfoxide (DMSO), lecithin and menthol at 5 and 10% levels were evaluated. In-vitro studies were performed with Franz Diffusion Cells using cellulose membrane and porcine ear skin as the diffusion barriers for 6 hours. The selected formulation with maximum drug release through cellulose membrane was then chosen for drug release through porcine ear skin.;Studies with cellulose membranes showed that release from cationic gel base release was superior to the nonionic gel base (Flux 0.07905 mg/cm 2hr and 0.01497 mg/cm2 hr respectively for 6.25% gel). The inclusion of additives at all levels had little or no effect in enhancing the drug release from these formulations. Among all the formulations tested, cationic gel base with 5% lecithin gave 2.6% drug release in 6 hour. The drug release of this formulation was then studied through porcine ear skin for 6 hours. Here, the drug release pattern remained similar to that observed with cellulose membrane, but the amount of total drug diffused was reduced as profiles. The Cationic gel base containing 5% lecithin with 12.5% of Promethazine hydrochloride gave the optimum release of drug. This study supports that with a proper composition of a dermatological vehicle, it is possible to develop a topical formulation with optimal drug release for a better clinical effect.