奥利司他胶囊有区分力溶出度检测法的建立及溶出曲线相似性评价

Establishment of a discrinatory dissolution method for orlistat capule and evalution of the similarity of dissolution curue

目的建立有区分能力的奥利司他胶囊溶出度检测法,评价国内6家企业与进口奥利司他胶囊溶出曲线的相似性。方法采用HPLC法,色谱柱为Thermo Hyersil GOLD C_(18)(150 mm×4.6 mm,5μm)柱,流动相为乙腈-水(85∶15),流速为1.0 mL·min^(-1),检测波长为195 nm,柱温为30℃,进样量为20μL。考察不同浓度十二烷基硫酸钠、不同浓度氯化钠及不同pH溶出介质对溶出曲线的影响,筛选出最佳溶出条件,并采用溶出曲线相似因子法评价溶出曲线的相似性。结果奥利司他在5.989~179.697μg·mL^(-1)范围内线性关系良好(r=0.999 8),平均回收率为100.4%,RSD为1.1%(n=9)。筛选出的最佳溶出条件如下:以含1.0%十二烷基硫酸钠、0.5%氯化钠、pH 6.0的磷酸盐缓冲溶液为溶出介质,在桨法、75 r·min^(-1)、介质1 000 mL的条件下开展溶出试验。国内仅1家企业产品与参比制剂的溶出曲线相似,其余5家企业产品与参比制剂相比溶出行为均不一致。结论该法能有效区分不同企业生产的奥利司他胶囊的溶出行为,对我国开展奥利司他胶囊仿制药质量与疗效一致性评价具有一定的参考意义。

Objective To establish a discriminative dissolution test method for orlistat capsules and evaluate the similarity of dissolution curves of 6 domestic enterprises and imported orlistat capsules.Methods The HPLC method was used,the chromatographic column was Thermo Hyersil GOLD C_(18) (150 mm×4.6 mm,5μm) column,the mobile phase was acetonitrile and water (85:15),the flow rate was 1.0 mL·min^(-1),the detection wavelength was 195 nm,the column temperature was 30℃,and the injection volume was 20μL.The effects of different concentrations of sodium dodecyl sulfate,different concentrations of sodium chloride and different pH dissolution media on the dissolution curve were investigated,and the best dissolution conditions were selected.The similarity of the dissolution curve was evaluated using the dissolution curve similarity factor method.Results Orlistat had good linear relationship within the range of 5.989-179.697μg·mL^(-1)(r=0.999 8),and its average recovery rate was 100.4%,with an RSD of 1.1%(n=9).The optimal dissolution conditions selected were as follows:the pH 6.0 phosphate buffer solution containing1.0%sodium dodecyl sulfate and 0.5%sodium chloride was as dissolution medium;the conduct dissolution tests conducted under conditions of paddle method,75 r·min^(-1) and medium 1 000 mL.Only one domestic enterprise had a similar dissolution curve between the product and the reference formulation,while the other five enterprises had inconsistent dissolution behavior between the product and the reference formulation.Conclusion This measurement method can effectively distinguish the dissolution behavior of products from different enterprises,and has certain reference significance to evaluate the consistency of the quality and efficacy of orlistat capsules in China.