Preparation and characterization of benzydamine hydrochloride-loaded lyophilized mucoadhesive wafers for the treatment of oral mucositis

Abstract

Chemo/radiotherapy-induced oral mucositis (OM) has painful ulcers that can impair patients' lives. This study aimed to develop and characterize (in vitro and in vivo) benzydamine (BNZ) freeze-dried mucoadhesive wafers from chitosan (CS) in combination with different hydrophilic polymers as a locally controlled delivery system for OM treatment. The porous (69–83%) optimum wafers (0.02–0.03 g and 3.2–4.3 mm) released 90–95% of their drug content over 8 h and demonstrated 40–53 g mucoadhesion strength. Mechanical evaluations of F1 (CS) and F14 (CS/HPMC (3:1)) selected formulations showed modulus of elasticity, tensile strength, and % elongation at break ranging from 0.2 to 0.3 MPa, 0.01–0.02 MPa, and 15–18%, respectively. The antimicrobial efficacy of BNZ-loaded wafers was significantly higher than drug-free ones. The extract solutions of the drug-free and BNZ-loaded wafers revealed 100 and 20% viability in human gingival fibroblasts (HGFs) exposure. In vivo analysis demonstrated that BNZ-loaded wafers represented a significant reduction in macroscopic evaluation of OM and histopathological tests compared to positive and negative controls and drug-free wafers. Conclusively, lyophilized F1 and F14 mucoadhesive wafers had acceptable structural, mechanical, and biological properties and might be promising drug delivery systems for OM.