Synthesis of Thiolated Chitosan as Matrix for the Preparation of Metformin Hydrochloride Microparticles

Thiolated chitosan is synthesized by reacting chitosan and cysteine as the carriersof thiol groups with 1-ethyl-3-(3-dimethylamino propyl) carbodiimide (EDAC) as catalyst.The properties of thiolated chitosan was then characterized, and being formulated withmetformin HCl and sodium tripolyphosphate (STPP) to form microparticles. MetforminHCl microparticles tested for drug release use type II dissolution tester (paddle).Statistical data analysis performed using one-way ANOVA test followed by t-testsignificance level of at least P <0.05. The results showed that thiolated chitosan formed aslightly yellowish white solid, distinctive smells, looks fibrous, soluble in acid, in water,and mixed with water to form transparent gels with high viscosity. Chitosan-cysteineconjugates synthesized by the addition of 50 mM EDAC has the highest content of thiolgroups of 265,169 μmol per 50 mg of conjugates. Mucoadhesive test in vitro using rotatingcylinder showed that thiolated chitosan with the addition of 50 mM EDAC was able toadhere to the fresh cow's intestine for more than 10 hours. Release profiles of MetforminHCl microparticles showed that the chitosan-cysteine conjugates can be used as a matrixfor the controlled release dosage forms. The lowest rate of drug release was found inmicroparticles using thiolated chitosan with the addition of 50 mM EDAC, seen at minute360, a drug that released of 26,256%. The release of metformin HCl from microparticles aremore likely to follow the kinetics of drug release according to Higuchi equation.