QBD-BASED DEVELOPMENT AND EVALUATION OF ENTERIC COATED MUCOADHESIVE MICROCAPSULES OF AMOXICILLIN TRIHYDRATE AS A NOVEL CHRONOTHERAPEUTIC APPROACH FOR TREATMENT OF BACTERIAL INFECTIONS

摘要

Objective: The present work entails design and characterization of enteric coated mucoadhesive microcapsules loaded with amoxicillin trihydrate as a novel chronotherapeutic approaches for the treatment and management of bacterial infection. Methods: The microcapsules were prepared by solvent evaporation technique using ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) as rate-controlling and mucoadhesive polymers, followed by a triple coating with Eudragit L100 as enteric coating polymer. Box-Behnken statistical design (BBD) was applied for optimization of formulations containing EC, HPMCK100M and Eudragit L100 as factors for selected responses like entrapment efficiency, mucoadhesive property and drug release in 24 h. The optimized microcapsules were also characterized for particle size, drug content, swelling index, mucoadhesive strength, and in vivo antiulcer activity. Results: The optimized microcapsules exhibited good entrapment efficiency, particle size and mucoadhesive property. FT-IR studies revealed that there was no drug-polymer interaction. SEM studies revealed that microcapsules were non-aggregated, spherical in shape and smooth appearance. In vitro drug release data from microcapsules was fitted to different kinetic models to explain release profiles. The correlation coefficient (r 2 ) value indicated that drug release followed Higuchi model. Analysis of variance (ANOVA) showed significant difference in the release of drug from all the prepared formulations at P 0.05 level. Accelerated stability study of optimized formulation (F4) upto 6 month showed there was no change in drug content and release characteristics during storage.