Centre Européen d'étude du Diabète, Bd René Leriche, F-67200 Strasbourg, France.
Int J Pharm. 2012 Jan 17;422(1-2):338-40. doi: 10.1016/j.ijpharm.2011.10.017. Epub 2011 Oct 13.
Targeting new oral drug formulations in the intestine has a broad applicability in animal studies. Enteric-coated capsules are gastroresistant and specific drug delivery systems useful for the evaluation of new pharmaceutical formulations during pre-clinical validations in rats. The purpose of this study was to develop and validate in a large-scale, reliable, reproducible capsules, to offer a safe and standardized duodenum-specific delivery system adapted for studies in rats. The reproducibility of the coating method, the coating layer uniformity and thickness, the external capsules integrity and their enteric properties after in vitro dissolution in simulated gastric and intestinal media were already evaluated and validated. This study presents the in vivo tests of the gastroresistance and of the location of the disintegration. Micro-computerized tomography and a pharmacokinetic study of acetaminophen-filled capsules showed that the enteric-capsules were resistant in the stomach with no apparent leak of the capsules, and were disintegrated in the early duodenum 1-1.5h after oral administration. A positive impact on the bioavailability of acetaminophen in coated capsules was attested. In conclusion, this work, developed with a rigorous pharmaceutical technology, presents a tool adapted for duodenum-specific delivery of new formulations in rats.
靶向肠道的新型口服药物制剂在动物研究中有广泛的适用性。肠溶胶囊具有胃耐受性和特定的药物传递系统，可用于在大鼠的临床前验证中评估新的药物制剂。本研究的目的是开发和验证一种大规模、可靠、可重复的胶囊，提供一种安全和标准化的十二指肠特异性传递系统，适用于大鼠研究。已经评估和验证了包衣方法的重现性、包衣层的均匀性和厚度、胶囊的外部完整性以及在模拟胃和肠介质中的体外溶解后的肠溶性。本研究介绍了胃耐受性和崩解位置的体内测试。微计算机断层扫描和对乙酰氨基酚填充胶囊的药代动力学研究表明，肠溶胶囊在胃中具有抗胃腐蚀性，胶囊没有明显泄漏，并且在口服后 1-1.5 小时在早期十二指肠中崩解。证明了对乙酰氨基酚在涂层胶囊中的生物利用度有积极影响。总之，这项工作采用严格的制药技术开发，为大鼠中新型制剂的十二指肠特异性传递提供了一种工具。
