TERBUTALINE TRANSDERMAL DELIVERY - PREFORMULATION STUDIES AND LIMITATIONS OF IN-VITRO PREDICTIVE PARAMETERS

A transdermal dosage form of terbutaline may be useful to prevent noct urnal wheezing by providing prolonged duration of action. It will also improve patient compliance and bioavailability. Controlled Input of t he drug would be an additional advantage as this will reduce the inter subject variablity. Preformulation studies were conducted to determine the feasibility of a transdermal dosage form of terbutaline. The drug solubility in propylene glycol was 6.3 mg mL(-1). The apparent partit ion coefficient (n-octanol/deionized-water, pH 6.5) of terbutaline was 0.03. A pH-partition coefficient (octanol/buffer) profile indicated t hat the partition coefficient values were 0.02, 0.05 and 0.4 in buffer s of pH 3, 7.4 and 9, respectively. The required drug flux through the human skin to attain therapeutic concentrations in the blood was calc ulated to be 3.3 mu g cm(-2) h(-1) for a 10-cm(2) transdermal delivery system. Rabbit, guinea-pig and human skin was tested as the penetrati on barrier using modified Franz diffusion cells. Terbutaline flux valu es through the rabbit and guinea-pig skin were 8.3 and 7.7 mu g cm h(- 1), respectively. The flux through human full-thickness skin and human epidermis were 0.6 and 3.6 mu g cm(-1) h. Azone (3% w/v), a skin pene tration enhancer, significantly increased the drug flux through all th e membranes tested. Based on these studies, transdermal delivery of te rbutaline appears to be promising.