In vitro release and diffusion studies of promethazine hydrochloride from polymeric dermatological bases using cellulose membrane and hairless mouse skin

The study was designed to investigate the feasibility of developing a trans dermal drug dosage form of promethazine hydrochloride (PMH). The in vitro r elease and diffusion characteristics of PMH from various dermatological pol ymeric bases were studied using cellulose membrane and hairless mouse skin as the diffusion barriers. These included polyethylene glycol (PEG), hydrox ypropyl methylcellulose (HPMC), cross-linked microcrystalline cellulose, an d carboxyl methyl cellulose sodium (Avicel(R) CL-611), and a modified hydro philic ointment USP. In addition, the effects of several additive ingredien ts known to enhance the drug release from topical formulations were evaluat ed. The general rank order for the drug release from these formulations usi ng cellulose membrane was observed to be PEG > HMPC > Avicel CL-611 > hydro philic ointment base. The inclusion of the additives had little or no effec t on the drug diffusion from these bases, except for the hydrophilic ointme nt formulation containing 15% ethanol, which provided a significant increas e in the drug release. However, when these formulations were studied for dr ug diffusion through the hairless mouse skin, the Avicel CL-611 base contai ning 15% ethanol exhibited the optimum drug release. The data also revealed that this formulation gave the highest steady-state-flux, diffusion, and p ermeability coefficient values and correlated well with the amount of drug release.