FORMULATION AND IN-VITRO EVALUATION OF POLYMERIC FILMS OF DILTIAZEM HYDROCHLORIDE AND INDOMETHACIN FOR TRANSDERMAL ADMINISTRATION

Ethylcellulose-polyvinyl pyrrolidone films containing diltiazem hydroc hloride and indomethacin were evaluated for their potential drug deliv ery at a controlled rate, using rat skin, to select a suitable formula tion for the development of transdermal drug delivery systems. The inf luence of film composition, initial drug concentration, and film thick ness on the in vitro drug release rate as well as drug permeation thro ugh rat abdominal skin were studied. Drug release studies were carried out employing the paddle over disk method and drug permeation through full thickness of the rat abdominal skill was tested using a modified Franz diffusion cell fastened with O-ring. The drug content of the fi lm decreased at an apparent first-order rate, whereas the quantity of drug released Mns proportional to the square root of time. The release rates of both drugs increased linearly with increasing drug concentra tion and polyvinyl pyrrolidone fraction in the film, but was found to be independent of film thickness. The increase in release rate may be due to leaching of hydrophilic fraction of the film former which resul ted in the formation of pores. It was also observed that the release o f drugs from the films followed a diffusion-controlled model at low dr ug concentrations. A burst effect was observed initially, however, at high drug loading levels, This may be due to rapid dissolution of the surface drug followed by the diffusion of drug through the polymer net work in the film. The in vitro skin permeation profiles shelved increa sed flux values with increase of initial drug concentration in the fil m and also with the concentration of polyvinyl pyrrolidone. From this study, it is concluded that the films composed of ethylcellulose:polyv inyl pyrrolidone:diltiazem hydrochloride (8:2:2) and ethylcellulose:po lyvinyl pyrrolidone:indomethacin (8:2:3) should be selected for the de velopment of transdermal drug delivery systems, using a suitable adhes ive layer and backing membrane, for potential therapeutic use.