Abstract This study aimed to synthesize a chitosan (CHI) derivative, chitosan-iodoacetamide (CHI-IA), with enhanced mucoadhesive properties and develop buccal mucoadhesive tablets of CHI-IA for local delivery of dextromethorphan (DXT). Mucoadhesive CHI-IA was synthesized by a chemical reaction between CHI and iodoacetic acid (IA) in different weight ratios. The synthesized CHI-IA was characterized by Fourier-transformed infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR) to confirm the chemical structure and assure successful synthesis. DXT was selected as the model drug to be incorporated into the matrix tablet to develop mucoadhesive buccal cough relief tablets. The mucoadhesive strength of the CHI-IA tablets was determined by a texture analyzer. Moreover, the drug content and the release characteristics of DXT from the mucoadhesive tablets were evaluated. The FT-IR and NMR spectra of CHI-IA indicated the conjugation of IA on the structure of CHI. The CHI-IA tablets exhibited a 4-time increase in mucoadhesion force compared with that of unmodified CHI. Moreover, a gradual release of DXT from the tablets was observed, and the release kinetics best fit with the Higuchi model (R2 = 0.9912). Therefore, the CHI-IA could be applied as the mucoadhesive carrier system for drug delivery. Keywords: Chitosan, Iodoacetic acid, Mucoadhesive, Buccal tablets, Dextromethorphan
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