基于甘草中2种成分同时测定的附子理中丸溶出行为研究

Dissolution behavior of Fuzi Lizhong pill based on simultaneous determination of two components in Glycyrrhizae Radix et Rhizoma

通过同时测定甘草苷、甘草酸2种成分的溶出度，对附子理中丸的溶出行为进行初步研究，为附子理中丸质量控制提供依据，同时为体内溶出行为研究奠定基础。建立附子理中丸中甘草苷、甘草酸的HPLC同时检测方法；测定5个厂家15个批次附子理中丸在不同时间点的2种有效成分的溶出量，并求算出累积溶出度、绘制累积溶出度曲线图；采用厶相似因子法，基于相同厂家评价不同批次所得溶出曲线的相似性，基于相同有效成分评价不同厂家溶出曲线的相似性；对溶出数据进行模型拟合以归属附子理中丸的溶出模型。以0．25％十二烷基硫酸钠作为溶出介质的溶出效果最为理想。附子理中丸中有效成分甘草苷、甘草酸的溶出基本同步，且溶出行为可持续到48h。厂家2～5的3批次之间溶出行为均相似，表明绝大多数厂家溶出行为的相似度较好。厂家1的3批间存在2种有效成分溶出不相似的情况。不同厂家有效成分的溶出数据拟合结果一致，均以Weibull模型为最佳。5个厂家15批次样品均在48h内持续溶出，表明“丸者缓也”的缓慢释放特征明显。溶出曲线相似情况总体较好，表明大多数厂家不同批次之间的制剂质量具有一定稳定性。不同厂家间的甘草苷、甘草酸溶出曲线相似度具有一定的差异性，可能由于不同厂家的药材或制剂生产工艺参数不一致造成的。

To preliminarily investigate the dissolution behavior of Fuzi Lizhong pill, provide the basis for its quality control and lay foundation for in vivo dissolution behavior by determining the dissolution rate of liquiritin and glycyrrhizic acid. High-performance liquid chromatography （HPLC） method for simultaneous content determination of the two active ingredients of liquiritin and glycyrrhizic acid in Fuzi Lizhong pill was established; The dissolution amount of these two active ingredients in fifteen batches of Fuzi Lizhong pill from five manufacturers was obtained at different time points, and then the cumulative dissolution rate was calculated and cumulative dissolu-tion curve was drawn. The similarity of cumulative dissolution curve of different batches was evaluated based on the same factory, and the similarity of cumulative dissolution curve of different factories was evaluated based on the same active ingredients. The dissolution model of Fuzi Lizhong pill based on two kinds of active ingredients was established by fitting with the dissolution data. The best dissolu- tion medium was 0.25% sodium lauryl sulfate. The dissolution behavior of liquiritin and glycyrrhizic acid in Fuzi Lizhong pill was basi- cally the same and sustained release in 48 h. Three batches of the factories （factory 2, factory 3, factory 4 and factory 5） appeared to be similar in dissolution behavior, indicating similarity in dissolution behavior in most factories. Two of the three batches from factory 1 appeared to be not similar in dissolution behavior of liquiritin and glycyrrhizic acid. The dissolution data of the effective ingredients from different factories were same in fitting, and Weibull model was the best model in these batches. Fuzi Lizhong pill in 15 batches from 5 factories showed sustained release in 48 h, proving obviously slow releasing characteristics ＂pill is lenitive and keeps a long-time efficacy＂ . The generally good dissolution behavior also suggested that quality of different batches from most factories was stable. The dissolution behavior of liquiritin and glycyrrhizic acid in different factories was different, suggesting that the source of medicinal materi- als and preparation technology parameters in five factories were different.