The Studies Of Chlorpromazne Hydrochloride Sustained Release Pellets

Chlorpromazine Hydrochloride (CPZ) which is representative of phenothiazine. It has been mainly used for schizophrenia,it also can control nausea and vomiting and other clinical purpose. In this dissertion, the study was aiming at the preparation of CPZ 24h sustained-released pellets and validation in vivo, consisting of preparation methods for pellets, the sustained- release coating process for pellets, stability, pharmacokinetics. Results show: the sustained-release pellets had good appearance and stability,the drug was able to release in vitro over 24h.UV spectrophotometry was used for in vitro assay during the studies of release and HPLC ultraviolet method was utilized to determine the CPZ content in pellets.The preformulation results showed that CPZ is easily soluble in water and various physiological pH solutions and the n-octanol/water partition coefficients increase with pH rising in various physiological pH solutions(P_apP:5.73-26.38).HPLC ultraviolet method and UV spectrophotometry were used to determine the absorption sites and kinetics of CPZ in intestinal segments by the means of in situ perfusion method in rats.The results showed that CPZ was well absorbed in the whole intestinal segments,and the mechanism of its intestinal absorption was passive diffusion.CPZ pellets were prepared by means of power layering on the centrifugal granulation equipment. Through the formulation filtration and process observation, it was proved that the yield of the objective pellets (20-24 mesh cut) was about 45% and the average CPZ content was 20%. The results suggested the yield rate and CPZ content of the pellets can not reach the expected goals.CPZ pellets were prepared by another method of extrusion-spheronizationinvestigation of process parameters and formulation variables and orthogonal design were used to optimize the experiment conditions. The yield of the objective pellets (20-24 mesh cut) was about 85% and the CPZ content was 40%.The method of extrusion-spheronization for preparing CPZ pellets was reliable and repeated.