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

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