Development and Evaluation of Lyophilized Thiolated-chitosan Wafers for Buccal Delivery of Protein

Annealed and non-annealed freeze-dried wafers from synthesised thiolated-chitosan have been developed and evaluated. Wafers were obtained by freeze-drying aqueous gels of the thiolated polymer incorporating per polymer weight, 10 % each of glycerol as plasticizer, D-mannitol as cryoprotectant and 50% BSA as model protein drug. The formulation was freeze-dried with or without the process of annealing. Texture analyzer was employed to investigate the in vitro mucoadhesive properties in tensile mode, residual moisture content by thermo-gravimetric analysis (TGA) while hydration capacity and drug release studies were performed in 0.1M PBS. Microscopic architecture was examined using scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) was employed for protein phase separation studies and conformational stability by attenuated total reflectance-Fourier transform infra-red spectroscopy (ATR-FTIR) and confirmed with Circular dichroism (CD). The annealing process led to wafers with increased ease of hydration, improved in vitro mucoadhesive characteristics and enhanced BSA release, without affecting the conformational stability of the protein due to the presence of a cryoprotectant. These results show the potential application of annealed freeze-dried thiolatedchitosan wafers for buccal mucosa delivery of protein based drugs. INTRODUCTION Chitosan (CS) (poly[-(1,4)-2-amino-2-deoxy-D -glucopiranose]) is a natural polymer obtained by deacetylation of chitin (Wu et al., 2009). Due to its biocompatibility and biodegradation properties (VandeVord et al., 2002), chitosan has been used primarily for the purpose of improved mucoadhesion, permeation enhancement and drug delivery (Agnihotri et al., 2004) via mucosal routes such as GI mucosa (Van Der Lubben et al., 2001; Read et al., 2005), buccal (Giunchedi et al., 2002), and ocular (De Campos et al., 2004). The mucoadhesive properties exhibited by chitosan have been further improved by derivatization to generate thiolated-chitosans. Factors that can alter the interaction between the polymer © 2012 Kwame Nkrumah University of Science and Technology (KNUST) Journal of Science and Technology, Vol. 32, No. 2 (2012), pp 46-55 46