Evaluating side‐by‐side diffusion models for studying drug supersaturation in an absorptive environment: a case example of fenofibrate and felodipine

OBJECTIVE: To test whether a side-by-side diffusion model is suitable for studying drug supersaturation in an absorptive environment. METHODS: The microD/P model and the microFLUX model, using a Caco-2 cell monolayer/PAMPA membrane as the permeation barrier, respectively, were compared in terms of robustness and ease of handling, while studying the drug supersaturation-precipitation-permeation interplay. Continuing with the best model, the impact of the acceptor media and the importance of studying drug supersaturation in a combined dissolution-permeation model, as compared to a simple dissolution model, were evaluated. KEY FINDINGS: The two models produced similar results in terms of supersaturation, precipitation and permeation. The microFLUX model was considered more robust and easier to handle based on its cell-free permeation system. Using the microFLUX model, it was found that an acceptor medium with a high surfactant concentration increased the amount of permeated drug. The effect of absorption on drug supersaturation was found to be dependent on the drug, and the tested level of supersaturation. CONCLUSION: The tested models were comparable; however, Caco-2 cell monolayers were considered too sensitive to be used to study drug supersaturation. Further studies are needed to evaluate the observed drug-dependent effects of absorption on drug supersaturation.