Biomimetic PVPA in vitro model for estimation of the intestinal drug permeability using fasted and fed state simulated intestinal fluids

摘要

A prerequisite for successful oral drug therapy is the drug’s ability to cross the gastrointestinalbarrier. Considering the increasing number of new chemical entities in modern drugdiscovery, reliable and fast in vitro models are required for early and efficient prediction ofintestinal permeability. To mimic the intestinal environment, use of biorelevant media mayprovide valuable information on in vivo drug permeation. The present study aims atimproving the novel biomimetic phospholipid vesicle-based permeation assay’s(PVPAbiomimetic) biorelevance by investigating the applicability of the biorelevant media;fasted state simulated intestinal fluid (FaSSIF) and fed state simulated intestinal fluid(FeSSIF). The FaSSIF and FeSSIF’s influence on the permeability of the model drugsacyclovir, indomethacin, griseofulvin and nadolol was then assessed. The barriers’ robustnessin terms of storage stability was also evaluated. The barriers were found to maintain theirintegrity in presence of FaSSIF and FeSSIF. The model drugs showed changes inpermeability in presence of the different simulated intestinal fluids that was in agreement withprevious reports. Moreover, the barriers showed improved storage stability by maintaining itsintegrity for 6 months. Altogether, this study moves the PVPAbiomimetic an important steptowards a better in vitro permeability model for use in drug development.