A non-invasive, low-cost study design to determine the release profile of colon drug delivery systems: A feasibility study

Maurer, M. J. M., Schellekens, R. C. A., Wutzke, K. D., Dijkstra, G., Woerdenbag, H. J., Frijlink, H. W., Kosterink, J. G. W. & Stellaard, F., Aug-2012, In : Pharmaceutical Research. 29, 8, p. 2070-2078 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

PURPOSE: Conventional bioavailability testing of dosage forms based on plasma concentration-time graphs of two products in a two-period, crossover-design, is not applicable to topical treatment of intestinal segments. We introduce an isotope dual-label approach ((13)C- and (15)N(2)-urea) for colon drug delivery systems that can be performed in a one-day, non-invasive study-design.

METHODS: Four healthy volunteers took an uncoated or a ColoPulse-capsule containing (13)C-urea and an uncoated capsule containing (15)N(2)-urea. In case of colon-release (13)C-urea is fermented and (13)C detected as breath (13)CO(2). Absorbed (13)C-urea and (15)N-urea are detected in urine.

RESULTS: C and (15)N in urine released from uncoated capsules showed a ratio of 1.01 ± 0.06. The (13)C/(15)N-recovery ratio after intake of a ColoPulse-capsule was constant and lower >12 h post-dose (median 0.22, range 0.13-0.48). The (13)C/(15)N-ratio in a single urine sample at t ≥ 12 h predicted the 24 h non-fermented fraction (13)C of <26 %. Breath (13)CO(2) indicated delayed (>3 h) release and a fermented fraction (13)C >54 %.

CONCLUSIONS: Breath and urine (13)C and (15)N data describe the release-profile and local bioavailability of a colon delivery device. This allows non-invasive bioavailability studies for evaluation of colon-specific drug delivery systems without radioactive exposure and with increased power and strongly reduced costs.

Original languageEnglish
Pages (from-to)2070-2078
Number of pages9
JournalPharmaceutical Research
Issue number8
Publication statusPublished - Aug-2012


  • Colon-delivery, Local bioavailability, Release profile, Stable isotope, Urea, carbon 13, carbon dioxide, drug, nitrogen 15, urea, adult, article, breath analysis, colon, controlled study, cost control, drug absorption, drug bioavailability, drug capsule, drug coating, drug delivery system, drug distribution, drug elimination, drug metabolism, feasibility study, female, fermentation, human, human experiment, isotope labeling, male, mathematical model, non invasive procedure, normal human, priority journal, pulsatile drug release, study design, urinalysis

ID: 5614263