Study On Chlorphenesin Carbamate Sustained-Release Pellets

Objective:The aim of this study was to develop a kind of Chlorphenesin Carbamate sustained-release pellets, which would reduce the dosing frequency, narrow the blood concentration fluctuation and be more convenient for patients to use.Its quality and stability studies were also investigated.Method:The High performance liquid chromatographic (HPLC) method and the Ultraviolet spectrophotometry (UV) method were conducted to assay the content and release rate of the drug. The CPC pellets were prepared by extrusion spheronization.The effects of independent process parameters on yield,roundness and friability of pellets were srudied.Orthogonal design was used to optimize the technology of preparing.Eudragit NE30D was used as coating material to prepare CPC sustained-release pellets in a fluid-bed equipment.The effects of process variables and formulation variables on pellets preparation were investigated.The formulation and technology of CPC sustained-release pellets were optimized.The qualitative and quantitative determination methods were established for the quality control of CPC pellets in capsule.A stability analysis method was developed with HPLC,including stress testing,accelerated testing and long-term testing.Results:The methods of HPLC and UV were established.Validation studies demonstrated that the methods possessed a linear UV response,good system precision and accuracy,high sensitivity and specificity for CPC.The methods could be used to determine the content and release of CPC in pellets.The pellets presented high yield,perfect sphericity and friability.The sustained-release pellets were coated with a combination of Eudragit NE30D.The influence factors on the release of CPC were investigated.The formulation and technology were optimized.The results demonstrated that coated pellets showed obviously sustain-release effects,and the drug release profiles in vitro followed first-order kinetics.Results of stability studies on sustained-release pellets of CPC showed that the pellets were stable when exposed to high temperature and light,but sensitive to high humidity.Both the accelerated testing and long-term testing indicated that the dosage form was stable,hardly with any change during the stability study.The results met with the requirements of Chinese Pharmacopoeia(edition2005).Conclusion:The UV and HPLC methods were simple and accurate to be used in vitro.CPC was prepared for sustained-release pellets by film coating technology according to some former studys of these processes.The formulation process in this study was both reasonable and repeatable,and it has pleasant stability.The results met the requirements of designed experiments and also achieved the requirements of quantification control for sustained-release preparation making.