Two-Stage Single-Compartment Models to Evaluate Dissolution in the Lower Intestine.

The purpose was to propose two-stage single-compartment models for evaluating dissolution characteristics in distal ileum and ascending colon, under conditions simulating the bioavailability and bioequivalence studies in fasted and fed state by using the mini-paddle and the compendial flow-through apparatus (closed-loop mode). Immediate release products of two highly dosed active pharmaceutical ingredients (APIs), sulfasalazine and L-870,810, and one mesalamine colon targeting product were used for evaluating their usefulness. Change of medium composition simulating the conditions in distal ileum (SIFileum ) to a medium simulating the conditions in ascending colon in fasted state and in fed state was achieved by adding an appropriate solution in SIFileum . Data with immediate release products suggest that dissolution in lower intestine is substantially different than in upper intestine and is affected by regional pH differences > type/intensity of fluid convection > differences in concentration of other luminal components. Asacol® (400 mg/tab) was more sensitive to type/intensity of fluid convection. In all the cases, data were in line with available human data. Two-stage single-compartment models may be useful for the evaluation of dissolution in lower intestine. The impact of type/intensity of fluid convection and viscosity of media on luminal performance of other APIs and drug products requires further exploration.