Transbuccal permeation of a nucleoside analog, dideoxycytidine: effects ofmenthol as a permeation enhancer

The use of a safe and effective permeation enhancer is paramount to the suc cess of a buccal drug delivery system intended for systemic drug absorption . The enhancing effects of menthol (dissolved in an aqueous buffer in the a bsence of co-enhancers) on buccal permeation of a model hydrophilic nucleos ide analog, dideoxycytidine (ddC), were investigated. In vitro transbuccal permeation of ddC was examined using freshly obtained porcine buccal mucosa . The experiments were carried out in side-bi-side flow through diffusion c ells. Permeation enhancement studies were performed with varying concentrat ions of 1-menthol dissolved in Krebs buffer solutions containing ddC. Parti tion coefficient experiments were carried out to probe into the mechanism o f permeation enhancing properties of 1-menthol and DSC studies were conduct ed to determine if there is a eutectic formation between ddC and 1-menthol at various concentrations. Permeation of ddC increased significantly (P<0.0 5) in the presence of 1-menthol independent of the concentration of the ter pene. The apparent 1-octanol/buffer partition coefficient (log K-p) of ddC was significantly (P<0.05) increased in presence of 1-menthol and was also independent of the enhancer concentration. However, the tissue/buffer parti tion coefficient (log K-p') data showed a concentration dependent increase of log K-p' in presence of 1-menthol. Since log K-p' is a measure of drug b inding to the tissue in addition to drug partitioning, binding of ddC to th e buccal tissue may provide an explanation for the concentration dependent increase in these values. (C) 1999 Elsevier Science B.V. All rights reserve d.