A novel technique for intraduodenal administration of drug suspensions/solutions with concurrent pH monitoring applied to ibuprofen formulations

摘要

Characterization of dissolution of solid suspended drug particles in vivo is important for developing biopredictive in vitro tests. Therefore, methods to gain deeper insights into particle dissolution in vivo are needed. The soft Bioperm intubation method, a well established tool for investigation of permeability, absorption, metabolism, and drug interactions at predefined locations in the gastroinstinal tract, was modified. The novel intubation method involved pump-controlled infusion of pharmaceutical suspensions as well as simultaneous pH monitoring. This technique was used in a proof of concept study in healthy humans. Plasma sampling and non-compartmental analysis allowed comparison of three different ibuprofen drug products, a solution and two suspensions with different particle size distribution, as well as two different infusion rates. Both a particle size effect and an effect of altering infusion rates on pharmacokinetic parameters were shown. Moreover, it was possible to monitor intestinal pH changes after intestinal infusion. Infusion of ibuprofen resulted in a pH drop that was quantified by the concept of Area Between Curves (ABC).