Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets
Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets
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DOI：
10.1371/journal.pone.0129076
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发表时间：
2015-07-15
期刊：
影响因子：
3.7
通讯作者：
Kosterink, Jos G. W.
中科院分区：
文献类型：
--
作者：
Maurer, Jacoba M.;Schellekens, Reinout C. A.;Kosterink, Jos G. W.
前言ColoPulse片是口服剂型领域的一项创新发展，其特点是回肠远端和结肠定位释放。以前的人体研究表明，阿司匹林在回肠-结肠区域释放，但胃肠道pH值与释放之间的关系尚未在体内得到实验证明。这些信息将完成ColoPulse片剂的体内释放情况。材料和方法使用双标记同位素策略对16名健康志愿者进行了ColoPulse片剂的释放研究。为了确定胃肠道的pH值曲线和转运时间，使用了IntelliCap系统。同时服用含有C-13-尿素的ColoPulse片剂和含有N-15(2)-尿素的非包衣速释片剂，并在3小时后提供标准早餐。在服用片剂五分钟后，吞服IntelliCap胶囊，并测量PH值，直到排泄到粪便中。采集呼吸和尿液样本进行同位素分析。结果12名受试者均可进行完整分析。C-13-尿素的中位生物利用度为82%(95%可信区间为74-94%，范围为61-114%)。基于同位素信号的延迟时间(5%C-13释放)为5：42 h(95%CI为5：18~6：18 h，范围为2：36~6：36 h)，与基于pH的结肠到达时间(CAT)差异无统计学意义(中位数5：42 vs 5：31 h，p=0.903)。在所有受试者中，在C-13从ColoPulse片剂中释放之前，其肠道pH值都达到了7.0。讨论和结论从IntelliCap系统和C-13同位素信号的综合数据可以得出结论，ColoPulse片剂在体内的释放与转运时间无关，而是在pH达到7.0之后发生在回结肠区域。这支持了我们早先的发现，并证实了ColoPulse系统是一种有前景的回肠远端和结肠靶向递送系统。
IntroductionColoPulse tablets are an innovative development in the field of oral dosage forms characterized by a distal ileum and colon-specific release. Previous studies in humans showed release in the ileo-colonic region, but the relationship between gastrointestinal pH and release was not experimentally proven in vivo. This information will complete the in vivo release-profile of ColoPulse tablets.Materials and MethodsRelease from ColoPulse tablets was studied in 16 healthy volunteers using the dual label isotope strategy. To determine gastrointestinal pH profiles and transit times the IntelliCap system was used. A ColoPulse tablet containing C-13-urea and an uncoated, immediate release tablet containing N-15(2)-urea were taken simultaneously followed by a standardized breakfast after three hours. Five minutes after intake of the tablets the IntelliCap capsule was swallowed and pH was measured until excretion in the feces. Breath and urine samples were collected for isotope analysis.ResultsFull analysis could be performed in 12 subjects. Median bioavailability of C-13-urea was 82% (95% CI 74-94%, range 61-114%). The median lag time (5% release of C-13) was 5: 42 h (95% CI 5: 18-6: 18 h, range 2: 36-6: 36 h,) There was no statistically significant difference between lag time based on isotope signal and colon arrival time (CAT) based on pH (median 5: 42 vs 5: 31 h p = 0.903). In all subjects an intestinal pH value of 7.0 was reached before release of C-13 from the ColoPulse tablet occurred.Discussion and ConclusionsFrom the combined data from the IntelliCap system and the C-13-isotope signal it can be concluded that release from a ColoPulse tablet in vivo is not related to transit times but occurs in the ileo-colonic region after pH 7.0 is reached. This supports our earlier findings and confirms that the ColoPulse system is a promising delivery system for targeting the distal ileum and colon.