Garbacz Grzegorz, Cadé Dominique, Benameur Hassan, Weitschies Werner
University of Greifswald, Institute of Pharmacy, Center of Drug Absorption and Transport, Felix-Hausdorff-Strasse 3, 17487 Greifswald, Germany; Physiolution GmbH, Walter-Rathenau-Strasse 49a, 17489 Greifswald, Germany.
Capsugel R&D, 10, rue Timken, 68027 Colmar, France.
Eur J Pharm Sci. 2014 Jun 16;57:264-72. doi: 10.1016/j.ejps.2013.08.039. Epub 2013 Sep 8.
Current compendial dissolution and disintegrating testing is unable to mimic physiological conditions affecting gastric drug release from immediate release dosage forms. In order to obtain more realistic data, a novel test setup was developed that we term a 'dynamic open flow through test apparatus'. It is based on the previously described dissolution stress test device and attempts to simulate the intra-gastric dissolution conditions pertinent to immediate release dosage forms administered under fasting conditions with respect to flow rates, intra-gastric temperature profiles and gastric motility. The concept of the dynamic open flow through test apparatus has been tested using five different types of hard capsules: conventional hard gelatin capsules (HGC), three hypromellose based capsules (Vcaps, Vcaps Plus and DRcaps) and pullulan based capsules (Plantcaps). These were of different sizes but all contained 100mg caffeine in each formulation, adjusted to avoid buoyancy by addition of excipient. When the capsules were stressed in the apparatus under the dynamic flow conditions applying mild pressure simulating gastric motility, release from release from Vcaps Plus, Vcaps and Plantcaps capsules was very well comparable to HGC. Capsules are usually swallowed with cold water and the temperature dependency of release from gelatin was noted as a significant factor, since heat exchange in the stomach is slow.
当前药典中的溶出度和崩解度测试无法模拟影响速释剂型胃内药物释放的生理条件。为了获得更真实的数据，开发了一种新颖的测试装置，我们称之为“动态开放式流通测试装置”。它基于先前描述的溶出度压力测试装置，试图模拟与空腹条件下给药的速释剂型相关的胃内溶出条件，包括流速、胃内温度分布和胃蠕动。使用五种不同类型的硬胶囊对动态开放式流通测试装置的概念进行了测试：传统硬明胶胶囊（HGC）、三种羟丙甲纤维素基胶囊（Vcaps、Vcaps Plus和DRcaps）以及支链淀粉基胶囊（Plantcaps）。这些胶囊尺寸不同，但每种制剂中均含有100mg咖啡因，并通过添加辅料进行调整以避免浮力。当胶囊在模拟胃蠕动的轻微压力下于动态流动条件下在该装置中受压时，Vcaps Plus、Vcaps和Plantcaps胶囊的释放与HGC非常可比。胶囊通常用冷水吞服，并且由于胃内的热交换缓慢，明胶释放的温度依赖性被视为一个重要因素。
