Design and evaluation of thiolated chitosan based mucoadhesive and permeation enhancing bilayered buccal drug delivery system

Abstract

The objective of this study was to increase the bioavailability of fluvastatin by developing bilayered buccal mucoadhesive compacts. This study also focuses on the mucoadhesive potential of some natural gums for improved mucoadhesion and transmucosal permeation of existing mucoadhesive polymers by certain modifications. Bilayered mucoadhesive compacts with one layer of drug and mucoadhesive polymer, and second, non medicated, non permeable layer of ethylcellulose and magnesium stearate was prepared using direct compression technique. Natural gums like tamrind and xanthan gum were evaluated for its mucoadhesive properties. The mucoadhesion along with permeation character of chitosan was enhanced by immobilization of thiol groups on its surface utilizing 2-iminothiolane (Trauts reagent). The resulting chitosan-4thio-butylamidine conjugate (chitosan 4-thiobutylamidine (TBA) conjugate) was evaluated for its mucoadhesion, permeation and release properties. Experimental data revealed a several fold higher mucoadhesive property of chitosan-TBA conjugate than unmodified chitosan along with good permeation properties. Release studies revealed that the sustained release of fluvastatin over several hours may be obtained by combining the chitosan TBA conjugate with natural gums like xanthan and tamrind gum. Also, the bioavailability studies indicated that bioavailability of fluvastatin was enhanced using the aforementioned drug delivery system. Thus, the potential of the aforementioned drug delivery device is promising and may be considered as a novel tool in order to improve the therapeutic efficacy of various drugs with shorter half life and poor bioavailability. Key words: Mucoadhesion, buccal drug delivery, bilayered compact, thiolated chitosan.