Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Int J Pharm. 2019 Jan 10;554:366-375. doi: 10.1016/j.ijpharm.2018.11.019. Epub 2018 Nov 8.
Up to 50% of Crohn's disease and ulcerative colitis patients suffer from ileo-colonic inflammation. Topically delivered budesonide is an effective treatment but in vitro as well as clinical data suggest that oral formulations currently used in clinical practice are not optimal to treat the ileo-colon. The aim of this in vitro study was to develop ileo-colonic-targeted zero-order sustained-release tablets containing 3 mg or 9 mg budesonide. Targeted delivery was achieved by coating the tablets with the ColoPulse technology (ColoPulse 3 mg or ColoPulse 9 mg, respectively). Tablets were tested in a 10-h gastrointestinal simulation system for site-specific release, zero-order release kinetics (R ≥ 0.950), release rate, and completeness of release (≥80%). Release profiles of the novel formulations were compared with Entocort, Budenofalk, and Cortiment (budesonide MMX). ColoPulse 3 mg and 9 mg were targeted to the simulated ileo-colon, budesonide release was complete and in a sustained zero-order manner, and both formulations complied with a 6-month accelerated stability study. None of the formulations currently used in clinical practice targeted the ileo-colon. These in vitro results are discussed in light of clinical data. ColoPulse 3 mg and 9 mg are novel interesting formulations for the treatment of the entire ileo-colon in inflammatory bowel disease.
多达 50%的克罗恩病和溃疡性结肠炎患者患有回肠结肠炎症。局部给予布地奈德是一种有效的治疗方法，但体外和临床数据表明，目前临床使用的口服制剂并不适合治疗回肠结肠。本体外研究旨在开发含有 3mg 或 9mg 布地奈德的回肠结肠靶向零级持续释放片剂。通过用 ColoPulse 技术（ColoPulse 3mg 或 ColoPulse 9mg，分别）对片剂进行包衣来实现靶向传递。在 10 小时胃肠道模拟系统中对片剂进行了测试，以进行特定部位释放、零级释放动力学（R≥0.950）、释放率和释放完整性（≥80%）。新型制剂的释放曲线与 Entocort、Budenofalk 和 Cortiment（布地奈德 MMX）进行了比较。ColoPulse 3mg 和 9mg 靶向模拟回肠结肠，布地奈德完全释放且呈持续零级释放，两种制剂均符合 6 个月的加速稳定性研究。目前临床使用的制剂均未靶向回肠结肠。根据临床数据对这些体外结果进行了讨论。ColoPulse 3mg 和 9mg 是治疗炎症性肠病整个回肠结肠的新型有趣制剂。
