厄贝沙坦氢氯噻嗪片体外溶出与人体吸收相关性初步研究

Study on the Relativity of Bioavailability and Dissolution Profile of Irbesartan-Hydrochlorothiazide tablets

目的初步探讨仿制制剂厄贝沙坦氢氯噻嗪片与参比制剂CoAprovel中厄贝沙坦的体外溶出曲线和体内生物利用度的关系。方法测定仿制制剂和参比制剂中厄贝沙坦在多个介质的溶出曲线,采用f2评价其匹配情况。测定44名健康志愿者口服仿制制剂与参比制剂后厄贝沙坦的血药浓度,评价其生物等效性。结果仿制制剂与参比制剂CoAprovel的厄贝沙坦在pH 1.0和pH 4.5介质中溶出匹配,在pH 4.5+0.4%SDS,pH 6.8,pH 6.8+0.5%聚山梨酯20介质中溶出不匹配。体内生物利用度等效。结论本试验中的厄贝沙坦在体外溶出与体内吸收不完全相关。

OBJECTIVE To investigate the relativity of dissolution profile in vitro and bioavailability of irbesartan of the irbesartan-hydrochlorothiazide tablets. METHODS The irbesartan dissolution profiles of generic product and reference product in different mediums were determined.）~ factor was used to evaluate the profiles. A single oral dose of generic product and reference product were given to 44 healthy volunteers in a randomized crossover study. Concentration of irbesartan in plasma was determined, and the results were evaluated accordingly. RESULTS The irbesartan dissolution profiles of generic product and reference product were similar in pH 1.0, pH 4.5 mediums, but were dissimilar in pH 4.5＋0.4%SDS, pH 6.8, pH 6.8＋0.5%Tween 20 mediums. The bioavailability was equivalent. CONCLUSION The in vitro dissolution behavior could only be reference for in vivo performance for this product.