酮咯酸氨丁三醇双相控释片的制备及处方优化  

Preparation and Prescription Optimization of Ketorolac Tromethamine Biphasic Controlled-Release Tablets

作　　者：石林 曾媛 刘辉 许宁宁 SHI Lin;ZENG Yuan;LIU Hui;XU Ningning(School of Pharmacy,Hubei University of Science and Technology,Xianning,Hubei,China 437100;Department of Pharmacy,Medical Support Center of the General Hospital of the Central Theater Command of the Chinese PLA,Wuhan,Hubei,China 430070;Medical Support Center of the General Hospital of the Central Theater Command of the Chinese PLA,Wuhan,Hubei,China 430070)

机构地区：[1]湖北科技学院药学院,湖北咸宁437100 [2]中国人民解放军中部战区总医院医疗保障中心药剂科,湖北武汉430070 [3]中国人民解放军中部战区总医院医疗保障中心,湖北武汉430070

出　　处：《中国药业》2023年第16期57-62,共6页China Pharmaceuticals

基　　金：中国人民解放军联勤保障部队应用基础研究项目[CLB21J015]。

摘　　要：目的制备酮咯酸氨丁三醇双相控释片并优化其处方。方法采用高效液相色谱法测定样品中酮咯酸氨丁三醇含量,并计算累积释放度。单因素考察速释层中填充剂、崩解剂、润滑剂及控释层包衣增重对样品体外释放行为的影响。以速释层总质量、速释层硬脂酸镁质量占比和控释层包衣增重为考察因素,1,16 h累积释放度和硬度为评价指标,采用Box-Behnken设计-效应面法优化其双相控释片处方,并验证。结果最优处方为速释层总质量为320 mg,以微晶纤维素(MCC)作填充剂、交联羧甲基纤维素钠(CCMC-Na)作崩解剂、4.4 mg硬脂酸镁作润滑剂,控释层包衣增重为14.4%时制备酮咯酸氨丁三醇双相控释片,所得制剂1 h累积释放度为19.14%,16 h累积释放度为93.58%,硬度为47 N。实测值与预测值偏差为-6.18%~1.08%。结论制成的酮咯酸氨丁三醇双相控释片具有临床所需的速效及长效的双相释放特性,是一种能有效缓解疼痛的新型制剂。Objective To prepare ketorolac tromethamine biphasic controlled-release tablets,and to optimize their prescription.Methods The content of ketorolac tromethamine in the samples was determined by the high-performance liquid chromatography(HPLC)method,and the cumulative release rate was calculated.The effects of filler,disintegrating agent,lubricant in rapid-release layer and coating weight gain of controlled-release layer on the in vitro release behavior of samples were investigated by the single factor test.The prescription of ketorolac tromethamine biphasic controlled-release tablets was optimized by the Box-Behnken design-response surface methodology,with the total mass of rapid-release layer,the mass proportion of magnesium stearate in rapid-release layer and the coating weight gain of controlled-release layer as the investigation factors,and with the one-hour,16-hour cumulative release rates and the hardness as the evaluation indicators.Then,the verification test was carried out.Results The optimal prescription of ketorolac tromethamine biphasic controlled-release tablets was as follows:the total mass of rapid-release layer was 320 mg,with microcrystalline cellulose(MCC)as the filler,cross-linked carboxymethylcellulose sodium(CCMC-Na)as the disintegrating agent,4.4 mg magnesium stearate as the lubricant,and the coating weight gain of controlled-release layer was 14.4%.The one-hour cumulative release rate of the prepared prescription was 19.14%,the 16-hour cumulative release rate was 93.58%,and the hardness was 47 N.The deviation between the measured value and the predicted value was in the range of-6.18%to 1.08%.Conclusion The prepared ketorolac tromethamine biphasic controlled-release tablets have the rapid and long-term biphasic release characteristics required for clinical treatment,which are new type of prescription that can effectively relieve pain.

关 键 词：酮咯酸氨丁三醇 双相控释片 制备工艺 累积释放度 响应面法 

分 类 号：R943[医药卫生—药剂学] R971.1[医药卫生—药学]