Dressman J B, Reppas C
Institute of Pharmaceutical Technology, J. W. Goethe University, Frankfurt am Main, Germany.
Eur J Pharm Sci. 2000 Oct;11 Suppl 2:S73-80. doi: 10.1016/s0928-0987(00)00181-0.
Although several routes of administration can be considered for new drug entities, the most popular remains the oral route. To predict the in vivo performance of a drug after oral administration from in vivo data, it is essential that the limiting factor to absorption can be modelled in vitro. In the case of BCS class II drugs dissolution is rate-limiting to absorption, so the use of biorelevant dissolution tests can be used to predict differences in bioavailability among different formulations and dosing conditions. To achieve an a priori correlation, the composition, volume and hydrodynamics of the contents in the gastrointestinal lumen following administration of the dosage form must be accurately simulated. Four media have been chosen/developed to model composition of the gastric and intestinal contents before and after meal intake. These are SGF, milk, FASSIF and FeSSIF, which model fasted and fed state conditions in the stomach and small intestine respectively. Using these media, excellent correlations have been obtained with the following poorly soluble drugs: danazol, ketoconazole, atovaquone and troglitazone. In all cases, fed vs. fasted state effects can be predicted from dissolution data and, where several formulations were available for testing, dissolution tests could also be used to determine which would have the best in vivo performance.
尽管新药实体可以考虑几种给药途径，但最常用的仍是口服途径。为了根据体内数据预测药物口服后的体内性能，至关重要的是吸收的限制因素能够在体外进行模拟。对于BCS II类药物，溶解是吸收的限速步骤，因此使用生物相关溶解试验可用于预测不同制剂和给药条件下生物利用度的差异。为了实现先验相关性，必须准确模拟剂型给药后胃肠道腔内内容物的组成、体积和流体动力学。已选择/开发了四种介质来模拟进餐前后胃和肠内容物的组成。它们分别是模拟胃液（SGF）、牛奶、空腹状态模拟小肠液（FASSIF）和进食状态模拟小肠液（FeSSIF），分别模拟空腹和进食状态下胃和小肠的情况。使用这些介质，已与以下难溶性药物获得了良好的相关性：达那唑、酮康唑、阿托伐醌和曲格列酮。在所有情况下，进食与空腹状态的影响均可从溶解数据中预测，并且在有多种制剂可供测试时，溶解试验也可用于确定哪种制剂在体内性能最佳。
