酮咯酸氨丁三醇口崩片处方优化及体外溶出度研究  

Optimization of Prescription and in Vitro Dissolution of Ketorolac Tromethamine Orally Disintegrating Tablets

作　　者：曾媛 张莹 徐亚君 刘辉 张国伟 ZENG Yuan;ZHANG Ying;XU Yajun;LIU Hui;ZHANG Guowei(The General Hospital of Central Theater Command,Wuhan,Hubei,China 430070;Macheng People′s Hospital,Huanggang,Hubei,China 438300;不详)

机构地区：[1]中国人民解放军中部战区总医院,湖北武汉430070 [2]湖北省麻城市人民医院,湖北黄冈438300 [3]不详

出　　处：《中国药业》2024年第3期63-68,共6页China Pharmaceuticals

摘　　要：目的优化酮咯酸氨丁三醇口崩片处方,并建立体外溶出度测定方法。方法以主观指标(口感、外观)、客观指标(硬度、崩解时间)为考察因素,采用模糊综合评分法联合L_(9)(3^(4))正交试验,对填充剂微晶纤维素(MCC)、甘露醇、崩解剂交联羧甲基纤维素钠(CCMC-Na)和硬脂酸镁用量进行优化,并验证处方工艺;采用高效液相色谱(HPLC)法测定酮咯酸氨丁三醇口崩片溶出度。结果酮咯酸氨丁三醇口崩片最佳处方为MCC 150 mg、甘露醇90 mg、CCMC-Na 10 mg、硬脂酸镁1.5 mg。制备的酮咯酸氨丁三醇口崩片口感良好,片面光洁,可压性强且硬度适中,崩解完全,且批间重复性良好。酮咯酸氨丁三醇质量浓度在1~100μg/mL范围内与峰面积线性良好(r=0.9999,n=5);平均回收率为98.76%,RSD为0.75%(n=9);精密度、稳定性、重复性试验结果的RSD均低于1.0%(n=6)。样品在10 min后即可溶解完全,溶出度均超过90%。结论优化的处方工艺简单、重复性好,可为酮咯酸氨丁三醇口崩片的工业化生产提供参考。Objective To optimize the prescription of Ketorolac Tromethamine Orally Disintegrating Tablets,and to establish a method for the determination of the in vitro dissolution.Methods Taking subjective indexes(taste,appearance)and objective indexes(hardness,disintegration time)as the factors,the dosage of filling agent microcrystalline cellulose(MCC),mannitol,disintegrating agent cross-linked carboxymethyl cellulose sodium(CCMC-Na)and magnesium stearate was optimized by using fuzzy comprehensive evaluation method combined with L_(9)(3^(4)) orthogonal test,and the prescription process was verified.The dissolution rate of Ketorolac Tromethamine Orally Disintegrating Tablets was determined by the high-performance liquid chromatography(HPLC)method.Results The optimal prescription of Ketorolac Tromethamine Orally Disintegrating Tablets was 150 mg of MCC,90 mg of mannitol,10 mg of CCMC-Na,and 1.5 mg of magnesium stearate.The prepared Ketorolac Tromethamine Orally Disintegrated Tablets had good taste,smooth surface,strong compressibility,moderate hardness,complete disintegration,and good inter-batch reproducibility.The linear range of ketorolac tromethamine was 1-100μg/mL(r=0.9999,n=5).The average recovery rate of ketorolac tromethamine was 98.76%with an RSD of 0.75%(n=9).The RSDs of precision,stability,and repeatability test results were all lower than 1.0%(n=6).The sample could be completely dissolved in the solvent after 10 min,with dissolution rates>90%.Conclusion The optimal prescription process is simple and reproducible,which can provide a reference for the industrial production of Ketorolac Tromethamine Orally Disintegrating Tablets.

关 键 词：酮咯酸氨丁三醇 口崩片 模糊综合评价法 L_(9)(3^(4))正交试验 溶出度 处方优化 

分 类 号：R971.7[医药卫生—药品] TQ460.6[医药卫生—药学] R917[化学工程—制药化工]