Study On Chlorphenesin Carbamate Sustained-Release Tablets

Objective:To prepare an oral sustained-release delivery system of Chlorphenesin Carbamate(CPC) and investigate its stability tentatively.Methods:Ultraviolet spectrophotometry (UV) method was developed for drug in vitro release of CPC sustained-release tablets. High performance liquid chromatography(HPLC) method was developed to determine content and related compounds of CPC sustained-release tablets.The method of wet preparation particle was developed for the preparation of CPC sustained-release tablets. The formulation and technology of CPC sustained-release tablets were investigated.In single factor experiments, the influence of bulking agents, binders, lubricants, particle sizes, hardness, and varietal release determination methods to release rates were investigated. On this basis, orthogonal design was used to optimize the formulations of the sustained-release tablets. Investigation the in vitro release behaviors of CPC sustained-release tablets with in vitro release rates as index. sustained-release tablets were produced according to the optimized formulation. Quality evaluations of sustained-release tablets had been finished, including appearance, content, release rate and related substance.Stability testings were carried out according to Guidance for Stability Testing of New drug substances and products of SFDA.Results:According to the single factor experiments, the conditions that the bulking agent was HPMC(E90), the binder was5%EC alcoholic solution, the lubricant was magnesium stearate, the particles should pass16mesh sieve,were determined.The optimum data of four factors were:HPMC(E90):100mg;5%EC alcoholic solution:25%; lactose:10mg; hardness:8kg.The UV and HPLC methods, which were monitored by methodology, were accurate and stable. The content of CPC was measured by HPLC method with a mixture of N-hexane:isopropyl alcohol:glacial acetic acid (850:150:1) as mobile phase, the content of CPC is in the range of98.0%～102.0%of marked quantity. The related substance of CPC was measured by the same method as the content. The release rate was measured by quant method, rotation rate was100r·min-1, about30%was released in2h, about50%was released in4h, and more than75%was released in7h. The drug release profile in vitro followed Higuchi kinetics. The in-vitro release rate followed requirements essentially.Under the conditions of4500±5001x and60℃, the appearance, release rate, content and related substance were stable; although, unstable to high humidity (90%±5%), during disposition, incremental quantity of sustained-release tablets was more than10%; under the conditions of humidity75%±5%, the appearance, release rate, content and related substance were stable. Result of the accelerated testing and the long-term testing showed that tablets were stable during disposition, when aluminum plastics package bag was used as package material.Conclusion:The prepared tablets were complied with the character of sustained-release tablets, and it has pleasant stability. The UV method,which was simple, and accurate, could to be used in-vitro release rate determination. HPLC method was excellent in specificity and accurate, could to be used in content and related substance determinations. The tablets were stable to illumination and high temperature, unstable to humidity. The tablets were stable in the acceleration and long-term testing when the packages were moisture resistant.