Institute of Pharmacy, University of Greifswald, Greifswald 17487, Germany.
Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland 21201, United States.
Mol Pharm. 2024 Jun 3;21(6):2828-2837. doi: 10.1021/acs.molpharmaceut.3c01241. Epub 2024 May 9.
Nefecon, a targeted-release capsule formulation of budesonide approved for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy, targets overproduction of galactose-deficient immunoglobulin A type 1 in the Peyer's patches at the gut mucosal level. To investigate whether the commercial formulation of Nefecon capsules reliably releases budesonide to the distal ileum, a human study was conducted with test capsules reproducing the delayed-release function of Nefecon capsules. Caffeine was included in the test capsules as a marker for capsule opening in the gut since it appears rapidly in saliva after release from orally administered dosage forms. Magnetic resonance imaging with black iron oxide was used to determine the capsule's position in the gut at the time caffeine was first measured in saliva and additionally to directly visualize dispersion of the capsule contents in the gut. In vitro dissolution results confirmed that the test capsules had the same delayed-release characteristics as Nefecon capsules. In 10 of 12 human volunteers, the capsule was demonstrated to open in the distal ileum; in the other two subjects, it opened just past the ileocecal junction. These results compared favorably with the high degree of variability seen in other published imaging studies of delayed-release formulations targeting the gut. The test capsules were shown to reliably deliver their contents to the distal ileum, the region with the highest concentration of Peyer's patches.
尼福康，一种布地奈德靶向释放胶囊制剂，获批用于减少原发性免疫球蛋白 A 肾病成人的蛋白尿，其作用靶点是在肠道黏膜水平的派伊尔氏结中，针对半乳糖缺乏的免疫球蛋白 A1 型的过度产生。为了研究尼福康胶囊的商业制剂是否能可靠地将布地奈德递送至回肠末端，进行了一项人体研究，使用复制了尼福康胶囊延迟释放功能的测试胶囊。由于咖啡因在口服剂型释放后会迅速出现在唾液中，因此它被包含在测试胶囊中作为胶囊在肠道中打开的标志物。使用带有黑色氧化铁的磁共振成像来确定胶囊在肠道中的位置，此时咖啡因首次在唾液中被测量，并且还可以直接观察胶囊内容物在肠道中的分散情况。体外溶解结果证实，测试胶囊具有与尼福康胶囊相同的延迟释放特征。在 12 名志愿者中的 10 名中，胶囊被证明在回肠末端打开；在另外两名受试者中，胶囊在回盲肠交界处打开。这些结果与针对肠道的其他已发表的延迟释放制剂的成像研究中观察到的高度变异性相比表现良好。测试胶囊被证明能够可靠地将其内容物递送至回肠末端，该区域派伊尔氏结的浓度最高。
