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 (¹³C- and ¹⁵N₂-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 ¹³C-urea and an uncoated capsule containing ¹⁵N₂-urea. In case of colon-release ¹³C-urea is fermented and ¹³C detected as breath ¹³CO₂. Absorbed ¹³C-urea and ¹⁵N-urea are detected in urine.

Results

C and ¹⁵N in urine released from uncoated capsules showed a ratio of 1.01?±?0.06. The ¹³C/¹⁵N-recovery ratio after intake of a ColoPulse-capsule was constant and lower >12?h post-dose (median 0.22, range 0.13?C0.48). The ¹³C/¹⁵N-ratio in a single urine sample at t ??12?h predicted the 24?h non-fermented fraction ¹³C of <26?%. Breath ¹³CO₂ indicated delayed (>3?h) release and a fermented fraction ¹³C >54?%.

Conclusions

Breath and urine ¹³C and ¹⁵N 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.