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

The use of a safe and effective permeation enhancer is paramount to the success of a buccal drug delivery system intended for systemic drug absorption. The enhancing effects of menthol (dissolved in an aqueous buffer in the absence of co-enhancers) on buccal permeation of a model hydrophilic nucleoside 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 cells. Permeation enhancement studies were performed with varying concentrations of 1-menthol dissolved in Krebs buffer solutions containing ddC. Partition coefficient experiments were carried out to probe into the mechanism of permeation enhancing properties of 1-menthol and DSC studies were conducted to determine if there is a eutectic formation between ddC and 1-menthol at various concentrations. Permeation of ddC increased significantly (P<0.05) in the presence of 1-menthol independent of the concentration of the terpene. 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 partition 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 binding to the tissue in addition to drug partitioning, binding of ddC to the buccal tissue may provide an explanation for the concentration dependent increase in these values. (C) 1999 Elsevier Science B.V. All rights reserved.