Khan M Zahirul I, Rausl Dragica, Zanoski Ruzica, Zidar Snjezana, Mikulcić Jasna Horvat, Krizmanić Lara, Eskinja Maja, Mildner Boris, Knezević Zdravka
PLIVA Research Institute Ltd, Zagreb, Croatia.
Biol Pharm Bull. 2004 Oct;27(10):1630-5. doi: 10.1248/bpb.27.1630.
Loratadine was studied both in vitro and in vivo (in healthy humans) to classify it according to the Biopharmaceutics Classification System (BCS) in order to gain more understanding of the reasons for its highly variable nature with respect to plasma time profiles, and to determine the most appropriate dissolution test conditions for in vitro assessment of the release profile of the drug from solid dose forms. Based on the solubility of loratadine determined under various pH conditions and its permeability through Caco-2 monolayers, loratadine was classified as a Class II drug. Plasma profiles were predicted by convolution analysis using dissolution profiles obtained under various pH and hydrodynamic conditions as the input function and plasma time data obtained from a syrup formulation as the weighting function. The predicted profiles based on dissolution studies done at gastric pH values were in reasonable agreement with the mean bio-data suggesting dissolution testing should be done at gastric pH values. However, the bio-data were highly variable and it is suggested this may be due, at least in part, to high individual gastric pH variability and dissolution occurring in the intestine on some occasions, and therefore, dissolution testing should also be done in simulated intestinal fluid.
对氯雷他定进行了体外和体内（在健康人体中）研究，以便根据生物药剂学分类系统（BCS）对其进行分类，从而更深入了解其血浆时间曲线高度可变的原因，并确定用于体外评估该药物从固体剂型中释放曲线的最合适溶出度测试条件。根据在各种pH条件下测定的氯雷他定溶解度及其透过Caco-2单层的渗透率，氯雷他定被归类为II类药物。通过卷积分析预测血浆曲线，使用在各种pH和流体动力学条件下获得的溶出曲线作为输入函数，以及从糖浆制剂获得的血浆时间数据作为权重函数。基于在胃pH值下进行的溶出度研究预测的曲线与平均生物数据合理一致，表明溶出度测试应在胃pH值下进行。然而，生物数据高度可变，建议这可能至少部分归因于个体胃pH值的高度变异性以及某些情况下在肠道中发生的溶解，因此，溶出度测试也应在模拟肠液中进行。
