基于渗透压原理实现尼莫地平可控释药系统的研究  

Research on Nimodipine Controlled Release Drug System Based on the Principle of Osmotic Pressure

作　　者：张文君[1] 马蕊 李沐谣 刘思怡 王立[1] ZHANG Wen-jun;MA Rui;LI Mu-yao;LIU Si-yi;WANG Li(School of Pharmaciutical Science,Harbin University of Commerce,Engineering Research Center of Natural Anti-Cancer Drugs,Ministry of Education,Heilongjiang Key Laboratory of Preventive and Therapeutic Drug Research of Senile Diseases,Harbin 150076,China)

机构地区：[1]哈尔滨商业大学药学院,抗肿瘤天然药物教育部工程研究中心,黑龙江省预防与治疗老年性疾病药物研究重点实验室,哈尔滨150076

出　　处：《中国药学杂志》2022年第9期718-728,共11页Chinese Pharmaceutical Journal

基　　金：2019年度哈尔滨商业大学“青年创新人才”支持计划资助(2019CX12)。

摘　　要：目的制备基于渗透压原理的尼莫地平渗透泵胶囊,考察影响其释药行为的因素,优化处方并考察其释放机制。方法根据尼莫地平渗透泵胶囊在体外累积释放度与零级方程拟合度,对囊壳、含药层、助推层的辅料种类和用量进行单因素考察,选出释放主要影响因素为致孔剂用量、含药层并检测其渗透压活性物质用量和膨胀剂用量,利用Box-Behnken设计法对其进一步优化,确定最优处方。制备3批尼莫地平渗透泵胶囊体外释放度与零级方程拟合考察其释药特性,再使用相似因子法(f_(2))进行释放机制研究。结果尼莫地平渗透泵胶囊最优处方为致孔剂(PEG 6000)用量14 mg、含药层渗透压活性物质(NaCl)用量33.7 mg、膨胀剂(PEO 800万)用量33.2 mg,制备的尼莫地平渗透泵胶囊在12 h内药物释放较完全,致孔剂为药物提供释药途径,渗透压活性物质为释药动力。结论尼莫地平渗透泵胶囊控释效果良好,累积释放度大于90%,并且接近零级释放方程,符合预期。OBJECTIVE To prepare nimodipine osmotic pump capsule based on osmotic pressure principle,and investigate the factors affecting its drug release behavior,prescription optimization and release mechanism.METHODS According to the fitting degree between the cumulative release rate of nimodipine osmotic pump capsule in vitro and the zero-order equation,the types and amounts of auxiliary materials in capsule shell,drug-containing layer and booster layer were investigated by single factor.The main influencing factors of release were pore-forming agent,osmotic pressure active substance and swelling agent.The Box-Behnken design was used to fit the model and determine the best prescription.Three batches of nimodipine osmotic pump capsules were prepared,and their release characteristics were investigated by fitting with the zero-order equation in vitro,and then the release mechanism was studied by similarity factor method(f_(2)).RESULTS In the optimal prescription of nimodipine osmotic pump capsule,the dosage of pore-forming agent(PEG 6000),osmotic pressure active substance(NaCl)and swelling agent(PEG 8000 thousand)were 14 mg,33.7 mg and 33.2 mg respectively.The drug release is relatively complete within 12 hours,indicating that the porogen is the drug release pathway and the active substance is the drug release power.CONCLUSION The nimodipine osmotic pump capsule prepared has a good controlled release effect.The cumulative release is greater than 90%,and it is close to the zero-order release equation,which is in line with expectations.

关 键 词：尼莫地平 渗透泵 释放机制 缓控释 BOX-BEHNKEN设计 

分 类 号：R944[医药卫生—药剂学]