Design and In Vitro Evaluation of A Novel Polymeric Excipient For Buccal Applications

Abstract

The objective of this study was to develop and evaluate a more effective mucoadhesive thiomer for buccal drug-delivery systems. 2-iminothiolane was covalently attached to a chitosan backbone. A preactivation step followed, mediated by 6,6´dithionicotinamide, thiol groups were modified by disulfide bonds formation. Mucoadhesion studies were performed on buccal mucosa. In addition, water-uptake capacity, disintegration, release and cytotoxicity studies were completed. The obtained chitosan-thiobutylamidine conjugate displayed 647.4 ± 85.23 µmol/g immobilized thiol groups. Due to the preactivation, approximately 60% of thiol groups were modified by formation of disulfide bonds. Chitosan-thiobutylamidine-mercaptonicotinamide displayed 1.8-fold higher stability and 1.6-fold higher mucoadhesive properties, respectively. The release study demonstrated a 1.4-fold more prolonged drug release compared with corresponding thiomers. According to these results, preactivated thiomers demonstrate an improved stability and increased mucoadhesive properties. Therefore, they seem to be advantageous for buccal administration over corresponding thiomers and chitosan.