Model Gut Platform, Institute of Food Research, Colney, Norwich NR4 7UA, UK.
Int J Pharm. 2011 Oct 31;419(1-2):192-9. doi: 10.1016/j.ijpharm.2011.07.046. Epub 2011 Aug 9.
The disintegration of a capsule shell may determine the onset of drug dissolution from capsule formulations. In this study, the release of a rapidly dissolving model drug (paracetamol), from two hydroxypropyl methylcellulose capsules containing either carageenan (HPMC-C) or gellan gum (HPMC-G) and one hard gelatin (HG) capsule, were investigated using a conventional in vitro model, the USP dissolution apparatus I, and a novel in vitro model of the human gastric compartment, the dynamic gastric model (DGM). The results obtained in vitro were compared with in vivo gamma scintigraphy human data and in vivo gastric emptying profiles available in the literature. The drug release from HPMC-G capsules, observed with the USP dissolution apparatus I, was delayed with respect to the other two capsules, while the results obtained from the DGM in the fasted state were closer together, which was in agreement with data from the in vivo studies. In the fasted state, the capsule rupture times obtained from the DGM were similar to those observed by gamma scintigraphy in vivo studies. In the fed state, the 'apparent' rupture times observed with the DGM were delayed compared to fasted, and were even longer than those observed by scintigraphy in vivo for HPMC-G and HG capsules. However, these discrepancies can reasonably be explained by considering the impact of food upon dispersion of the capsule contents and the sampling from the DGM, when compared to the human scintigraphy experiments.
胶囊壳的崩解可能决定药物从胶囊制剂中溶解的开始时间。在这项研究中，使用传统的体外模型（USP 溶解仪 I）和新型的人体胃腔体外模型（动态胃模型（DGM））研究了两种含有卡拉胶（HPMC-C）或结冷胶（HPMC-G）的羟丙基甲基纤维素胶囊和一种硬明胶（HG）胶囊中快速溶解模型药物（扑热息痛）的释放情况。将体外获得的结果与体内γ闪烁扫描人体数据和文献中可用的体内胃排空曲线进行了比较。用 USP 溶解仪 I 观察到 HPMC-G 胶囊的药物释放比其他两种胶囊延迟，而在空腹状态下从 DGM 获得的结果则更接近，这与体内研究的数据一致。在空腹状态下，从 DGM 获得的胶囊破裂时间与体内γ闪烁扫描研究观察到的相似。在进食状态下，与空腹相比，DGM 观察到的“表观”破裂时间延迟，对于 HPMC-G 和 HG 胶囊，甚至比体内闪烁扫描研究观察到的还要长。然而，当将 DGM 与人体闪烁扫描实验进行比较时，考虑到食物对胶囊内容物分散和从 DGM 取样的影响，这些差异可以得到合理的解释。
