6种市售奥美拉唑胶囊在模拟胃酸环境下的稳定性研究

 目的体外评价6种市售奥美拉唑肠衣颗粒的酸稳定性。方法建立测定奥美拉唑的HPLC；测定奥美拉唑胶囊的含量、释放度,通过改变溶出液的pH(pH1.2～7)，测定奥美拉唑在不同pH中溶出的剩余累积浓度，以及测定奥美拉唑标准品在pH2～5的5种pH环境中的剩余原形药物浓度及可能的分解产物的峰高；采用方差分析法对奥美拉唑溶出的累积剩余浓度进行统计学分析。结果6种市售奥美拉唑胶囊的含量及释放度均符合国家药品标准及药典规定，但体外模拟胃酸环境下的稳定性研究结果表明，除洛赛克外，其余5厂家产品均在pH＜6(pH3～5.5)即开始溶出，pH7时奥美拉唑肠衣颗粒的平均溶出的累积剩余浓度，6厂家产品之间存在显著性差异(P＜0.01)，A，E，B，C，F和D溶出的累积剩余浓度依次为：(136.16±7.85)，(127.73±6.54)，(118.69±5.93)，(105.25±11.94)，(87.88±5.89)和(73.69±5.88) μg·mL_-1；奥美拉唑标准品在pH2的环境中，1 min的原形药物浓度为初始浓度的54.70%，分解迅速。结论由于各厂家的处方及制备工艺不同，若采用胃管给药，不同厂家奥美拉唑胶囊的生物利用度及疗效可能不同。

In vitro evaluation of dissolution and stability of omeprazole in enteric-coated pellets

OBJECTIVE To evaluate the in vitro dissolution and stability of omeprazole in enteric-coated pellets from six manufacturers.METHOD S A HPLC method for the determination of omeprazole was developed.The brand product (A,Losec) was the reference in comparison to five generic products (B,C,D,E,F).The content of omeprazole,the percentage of omeprazole dissolved from the pellets, the in-vitro release profiles generated by changing the pH of the dissolution medium,and the amount of its main degradation product were measured respectively.Statistical analysis was carried out using the ANOVA test.RESULTS The content and percentage of omeprazole dissolved from the pellets were up to the drug standard (issued by SDA).There was statistical significant differences among the results of the in-vitro release profiles of the six manufacturers (P＜0.01);all of them began to release at pH ＜ 6 (from pH3～5.5) except Losec,and the accumulative concentrations at the end of the test were (136.16±7.85),(127.73±6.54),(118.69±5.93),(105.25±11.94),(87.88±5.89) and (73.69±5.88) μg·mL_-1(mean±SD) for the reference and products E,B,C,F and D,respectively.The omeprazole decomposed quickly at pH2,the concentration after one minute was 54.70% of the beginning concentration.CONCLUSION If the omeprazole enteric-coated granules were administered by the nasogastric tube,due to the formulation and preparation technology used by each manufacturer,the bioabailability and therapeutic effect of these products may be affected by their different dissolution characteristics from the pellets at different pH.