| The biopolymer chitosan is obtained by alkaline deacetylation of chitin, which is one of the most abundant polysaccharides in nature. Chitosan is a polysaccharide consisting of copolymers of glucosamine and N-acetylglucosamine. Chitosan was used, since it exhibits several favorable properties such as biodegradability, non-toxicity and biocompatibility. Besides, as a excipient, chitosan has multifunction such as anti-acid, anti-ulcer, anti-bacterial and anti-inflammatory, promote wound healing, blood lipid and cholesterol-lowering,and other anti-tumor effect. Therefore, the preparation of chitosan microspheres used as a drug carrier is better than other materials.To further enhance the solubility of this polymer and improve its mucoadhesive and/or permeation enhancing properties, various derivatives such as chitosan thioglycolic acid conjugates(TGA)were developed. These thiolated chitosans have numerous advantageous features in comparison to unmodified chitosan, such as significantly improved mucoadhesive and permeation enhancing properties.The aim of this study was to synthesize and evaluate the new topics adhesive materials of chitosan-TGA,select amoxicillin as model drug,prepare chitosan-TGA mucoadhesive microspheres, study the mucoadhesive properties, drug release and physical chemistry properties of the microspheres.The first part Preparation and analysis of chitosan-TGA By sulfhydryl acid and chitosan's amino reaction prepared chitosan-TGA, using titration to determinate the sulfhydryl content, sulfhydryl content is 978.6μmol/g, using infrared analysis to observe the structural changes. Preparation obtained chitosan-TGA was white fibrous solids, soluble in aqueous solution pH below 5, and water swelling can create transparent, high-viscosity gel.The second part Study on material's adhesion and impact factors Using Cp934p, chitosan and chitosan-TGA as adhesive material. in vitro adhesion force, adhesion time and the swelling rate were determined by home-made apparatus. Compared with chitosan ,the adhesion of chitosan-TGA increased 4.3 times, adhesion time increased 2.6 times, swelling rate no obvious changes; Compared with Cp934p,the adhesion of chitosan-TGA increased 1.5 times, adhesion time increased 3.4 times, but the swelling rate not higher than Cp934p.The third part Pharmaceutical studies of chitosan-TGA microspheres Chitosan-TGA mucoadhesive microspheres were prepared through emulsion-solvent evaporation method. Using the single factor and orthogonal design to optimize the prescription and preparation, the result as following: chitosan-TGA: drug is 7:3, emulsifier is 1%, temperature is 25℃, stirring speed is 800rpm, stirring time is 8 hours,.The fourth part Properties and quality studies of chitosan-TGA microspheres Optical microscopy observed that the microspheres were uniform spherical. Malvern laser diffraction measured microspheres the size range of 20-54μm. Gas chromatography measured microspheres hexane,methanol organic solvent residues below the Pharmacopoeia prescribed limits. HPLC determinated amoxicillin drug loading is 36.6±0.92%, encapsulation efficiency is 81.6±0.70%. Microspheres release curve accord with Hixson-Crowell model, drug release through the dissolution and diffusion. The study prepared chitosan-thioglycolic acid conjugates by sulfhydryl acid and chitosan's amino reaction, and its sulfhydryl content is 978.6μmol/g. Compared with chitosan ,the adhesion of chitosan-TGA increased 4.3 times, adhesion time increased 2.6 times, swelling rate no obvious changes.Currently, we have not yet discovered the reports of chitosan-TGA mucoadhesive microspheres. Our studies choose amoxicillin as model drug, selected the best prescription and preparation of chitosan-TGA microspheres by pharmaceutical studies firstly. Prepared microspheres the size range of 20-54μm, hexane, methanol organic solvent residues complianced the Pharmacopoeia, amoxicillin drug loading was 36.6±0.92%, encapsulation efficiency was 81.6±0.70 % , drug release curve accorded with Hixson-Crowell model.
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