吡喹酮植入剂制备及体外释放研究.docVIP

吡喹酮植入剂的制备及体外释放的研究 程亮，郭圣荣* 上海交通大学药学院，上海 200240 摘要：目的 制备吡喹酮（PZQ）植入剂并对其体外释放进行考察。方法 采用热熔融挤出法，以聚己内酯（PCL）及聚乙二醇1500（PEG1500）为基质材料制备吡喹酮植入剂，并用NMR、HPLC、XRD、FSEM对药物在制备过程中的热稳定性、药物在植入剂中的含量均匀度、药物在植入剂中的物理状态及植入剂释放前后的形貌进行了考察 结果 药物在制备过程中没有发生分解，药物的含量均匀度均在80％～120％的规定范围，药物的结晶度随着PEG1500含量的增加而不断降低，药物的释放速度随着PEG1500含量的增加而不断加快，体外释放符合Higuchi释放模型。结论 热熔融挤出法制备吡喹酮植入剂工艺可行，药物的释放可以通过改变PEG1500含量进行调节。 关键词：吡喹酮；聚己内酯；聚乙二醇；植入剂；体外释放 中图分类号： 文献标识码： 文章编号： Study on preparation and in vitro drug release of praziquantel implants Cheng Liang, Guo Sheng-rong Pharmacy school of shanghai jiaotong university, Shanghai 200240 Abstract: OBJECTIVE To prepare praziquantel implants and investigate the in vitro drug release. METHODS Praziquantel-contained implants were fabricated by hot-melting extrusion, and PCL、PEG1500 were chosen as the matrix. The thermal stability of PZQ during the process was analyzed by NMR; the drug content uniformity was determined by HPLC; the physical state of PZQ in the implants was studied using XRD; the surface and cross-sectional morphology of implants were observed by SEM. RESULTS PZQ was stable during the fabrication process; the drug was dispersed uniformly in the implants and the drug content uniformity was in the range of 80％～120％; with the increasing content of PEG1500 in the implants, the drug release rate was accelerated and the crystalline of PZQ was depressed; the in vitro drug release was fitted well with Higuchi equation. CONCLUSION The hot-melting extrusion method is feasible to prepare praziquantel-contained implants, the in vitro drug release can be adjusted by changing the content of PEG1500. Key Words: praziquantel; Polycaprolactone; Polyethylene; implants; in vitro drug release 包虫病（Hydatid disease）又称为棘球蚴病，是由棘球属绦虫引起的人畜共患寄生虫病。我国包虫病的分布主要在西北省份的畜牧区，调查显示在上述地区此病的发病率约为1‰～1％[1]。目前，包虫病的治疗手段为手术治疗和化学治疗：手术治疗的成本及危险性较高，同时该方法对医疗条件的要求也较高，故在西北牧区难以普及；化学治疗具有给药方便、成本低廉、安全有效等优点，故为我国治疗包虫病的首选方案。但是，传统的给药方式，即口服给药，依旧存在几点不足：ⅰ.药物的水溶性较差，口服药物后，部分药物因不能完全溶解而无法吸收；ⅱ.由于肝首过效应，经肠道吸收的药物，大部分被代谢成无药理活性的产物，致使药