Grimm Michael, Rump Adrian, Kromrey Marie-Luise, Morof Felix, Dumont Camille, Jannin Vincent, Tzvetkov Mladen Vassilev, Weitschies Werner
Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, 17489 Greifswald, Germany.
Department of Diagnostic Radiology and Neuroradiology, University Hospital Greifswald, 17475 Greifswald, Germany.
Pharmaceutics. 2023 Nov 3;15(11):2576. doi: 10.3390/pharmaceutics15112576.
Ready-to-fill enteric hard capsule shells are an evolving field of oral drug and nutraceutical products. Lonza Capsugel Enprotect capsules were recently proven to provide reliable release in the small intestine after fasted intake, but robustness against postprandial intake needed to be proven. In this study, the capsules were administered to 16 healthy young subjects after intake of a light meal. The Enprotect capsules were labelled with 5 mg black iron oxide and 25 mg C-caffeine. Magnetic Resonance Imaging was used to identify the localization and visual dispersion of the capsule filling. The salivary appearance of caffeine was considered a second independent and sensitive marker for the initial release. Whereas the fasted gastric residence time of the capsules amounted to 43 ± 32 min, it was increased to 158 ± 36 min after postprandial intake. Therefore, the mean dispersion time according to MRI and the mean caffeine appearance time were increased to 196 ± 37 min and 189 ± 37 min, respectively. But, similar to fasted administration, no capsule disintegration or leakage was observed in the stomach and 38% of the capsules disintegrated in the jejunum and 62% in the ileum. The mean dispersion time after gastric emptying and the mean caffeine appearance time after gastric emptying amounted to 38 ± 21 min and 31 ± 17 min, respectively. Both did not relevantly change compared to the fasted intake. Only the absolute dispersion time and caffeine appearance were prolonged due to the increased gastric residence and no relevant influence of the light meal was observed on the disintegration or release behavior of Enprotect capsules after gastric emptying. The capsules also showed robust enteric properties after postprandial administration.
即填型肠溶硬胶囊壳是口服药物和营养保健品领域一个不断发展的方向。龙沙卡普速吉尔Enprotect胶囊最近被证明在空腹服用后能在小肠中实现可靠释放,但餐后服用时的稳定性仍有待验证。在本研究中,让16名健康的年轻受试者在进食少量食物后服用这些胶囊。Enprotect胶囊用5毫克黑色氧化铁和25毫克C -咖啡因进行了标记。采用磁共振成像来确定胶囊填充物的定位和可视化分散情况。咖啡因在唾液中的出现被视为初始释放的第二个独立且敏感的标志物。空腹时胶囊在胃内的停留时间为43±32分钟,餐后服用后增加到158±36分钟。因此,根据磁共振成像得出的平均分散时间和咖啡因出现的平均时间分别增加到196±37分钟和189±37分钟。但是,与空腹给药类似,在胃内未观察到胶囊崩解或渗漏,38%的胶囊在空肠中崩解,62%在回肠中崩解。胃排空后的平均分散时间和胃排空后的咖啡因出现平均时间分别为38±21分钟和31±17分钟。与空腹服用相比,两者均无显著变化。只是由于胃停留时间增加,绝对分散时间和咖啡因出现时间延长,且未观察到少量食物对胃排空后Enprotect胶囊的崩解或释放行为有相关影响。餐后给药后,这些胶囊也显示出强大的肠溶特性。