Chitosan coated hydroxypropyl methylcellulose-ethylcellulose shell based gastroretentive dual working system to improve the bioavailability of norfloxacin

Abstract

This investigation was aimed to formulate, evaluate and optimize a gastroretentive dual working system based on mucoadhesion and floating mechanisms to improve the bioavailability of norfloxacin (NFX). Floating microballoons (FMB) were prepared by a non-aqueous emulsification–solvent evaporation method employing hydroxypropyl methylcellulose (HPMC) and ethylcellulose (EC) to develop a core matrix. Furthermore, FMB were coated with chitosan by an ionotropic gelation method to impart mucoadhesive characteristics. Prior to incorporation of NFX into mucoadhesive floating microballoons (MFMB), a solid dispersion (SD) of NFX was prepared using a spray–freeze drying method in order to improve the solubility of NFX. The morphological characteristics of the microballoons were assessed using scanning electron microscopy (SEM) which revealed the spherical shape of the microballoons with a smoother, dense and less porous surface. The developed microballoons were evaluated for various physicochemical parameters such as particle size, surface morphology, entrapment efficiency (EE), in vitro-dissolution, in vitro buoyancy and mucoadhesion. The optimized microballoons were developed with good in vitro-buoyancy coupled with high EE. Microballoons exhibited a zero-order release in simulated gastric fluid (SGF) demonstrating drug release in the range from 64.99 ± 3.26 to 99.94 ± 8.45% after 10 h through various formulations. Chitosan coating over FMB imparted excellent mucoadhesion in rat gut wall and results were also supported by mucin glycoprotein assay. MFMB were able to achieve higher mean plasma concentrations compared to FMB and pure NFX in Wistar rats. Keeping in mind the comprehensible advantages of a developed gastroretentive dual working system over a conventional gastroretentive drug delivery system, it can be concluded that the developed system can be used to target drugs in the gastric cavity.