A Non-Invasive, Low-Cost Study Design to Determine the Release Profile of Colon Drug Delivery Systems: A Feasibility Study

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 (C-13- and N-15(2)-urea) for colon drug delivery systems that can be performed in a one-day, non-invasive study-design. Four healthy volunteers took an uncoated or a ColoPulse-capsule containing C-13-urea and an uncoated capsule containing N-15(2)-urea. In case of colon-release C-13-urea is fermented and C-13 detected as breath (CO2)-C-13. Absorbed C-13-urea and N-15-urea are detected in urine. C and N-15 in urine released from uncoated capsules showed a ratio of 1.01 +/- 0.06. The C-13/N-15-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 C-13/N-15-ratio in a single urine sample at t a parts per thousand yen12 h predicted the 24 h non-fermented fraction C-13 of < 26 %. Breath (CO2)-C-13 indicated delayed (> 3 h) release and a fermented fraction C-13 > 54 %. Breath and urine C-13 and N-15 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.