替比培南酯缓释片的制备及体外释放特性考察

替比培南酯缓释片的制备及体外释放特性考察

程金来，陈小伟，丁兵

(鲁南制药集团股份有限公司，国家手性制药工程技术研究中心，山东 临沂 276006)

摘要：目的制备替比培南酯缓释片并对其体外释药特性进行研究。方法选用羟丙甲纤维素K4M、羟丙甲纤维素K15M为缓释骨架材料制备替比培南酯缓释片。采用正交设计法，以药物体外累积释放百分率为考察指标优化处方。结果制备的缓释片具有明显的缓释特征，体外释放符合一级释药动力学方程,释药机制为非Fick扩散。结论制备的替比培南酯缓释片具有较理想的体外缓释效果。

关键词：替比培南酯；缓释片；正交设计；释放度

作者简介：程金来，男，研究方向：新药研发，E-mail：chyuxuan2010@163.com

中图分类号：R944.9文献标识码：A

Preparation and release characteristics of Tebipenem Pivoxil Sustained-release Tablets

CHENGJin-lai,CHENXiao-wei,DINGBing

(LunanPharmaceuticalGroupCo.,Ltd.,NationalEngineeringandThecnologyResearchCenter

ofChiralityPharmaceutical,Linyi276006,China)

Abstract：ObjectiveTo prepare Tebipenem Pivoxil Sustained-release Tablets and investigate the drug release mechanism in vitro.MethodsHPMC K4M and HPMC K15M were used to prepare Tebipenem Pivoxil Sustained-release Tablets as matrix materials.Using the accumulative dissolution in vitro at different sampling time as the evaluation index,the formulation was optimized by the orthogonal design test.ResultsThe optimal formulation had a remarkable sustained-release property,the drug release profile in vitro followed first order kinetics,of which the mechanism was non-Fick diffusion.ConclusionThe prepared tablets exhibited more ideal sustained-release characteristics in vitro.

Key words:Tebipenem pivoxil;Sustained-release tablets;Orthogonal design;Dissolution

替比培南酯(Tebipenem pivoxil)为碳青霉烯类抗生素[1]，最早由美国辉瑞公司开发，日本明治制药株式会社研制的替比培南酯细粒剂于2009年在日本上市，适用于治疗对青霉素敏感或耐药肺炎链球菌和流感嗜血杆菌所致感染，尤其是儿科患者耳、鼻、喉和上呼吸道感染[2,3]。目前，用于成人上呼吸道和耳鼻喉感染治疗的临床研究也正在进行。替比培南酯的抗菌谱广、活性强，对大多数临床分离的菌株均表现出比青霉素及头孢类抗生素更强的抗菌性。与其它注射用碳青霉烯类抗生素相比，也表现出同等或更强的抗菌活性[4]。替比培南酯细粒剂为速释制剂，单次口服血药浓度达峰时间约为0.7 h，半衰期约为1 h，每日需服要两次。替比培南酯为时间依赖型抗生素，血药浓度大于最小抑菌浓度(MIC)时间越长，杀菌效果越好。……