Along with the increasing demand for candidate-enabling formulations comes the need for appropriate in vitro bioavailability forecasting. Dissolution/permeation (D/P) systems employing cell-free permeation barriers are increasingly gaining interest, due to their low cost and easy application as passive diffusion bio-predictive profiling in drug product development, as this accounts for nearly 75% of new chem. entities (NCEs) absorption mechanism. To this end, this study comprises theor. considerations on the design and exptl. work towards the establishment and optimization of a PermeaLoop based dissolution/permeation assay to simultaneously evaluate the drug release and permeation using Itraconazole (ITZ)-based amorphous solid dispersions (ASD) formulations, with different drug loads, based on a solvent- shift approach. Alternative method conditions were tested such as: donor medium, acceptor medium and permeation barrier were screened using both PermeaPad and PermeaPlain 96-well plates. A range of solubilizers, namely Sodium Dodecyl Sulfate, Vitamin E- TPGS and hydroxypropyl-β-cyclodextrin, were screened as possible solubilizing additives to the acceptor medium, while donor medium was varied between blank Fa SSIF (phosphate buffer) and FaSSI F. The method optimization also included the ITZ dose selection, being the ITZ single dose (100 mg) considered the most adequate to be used in further experiments to allow the comparison with in vivo studies. In the end, a standardized approach that may be applied to predict the bioavailability of weakly basic poorly soluble drug-based formulations is described, contributing to strengthening the anal. portfolio of in vitro pre- clin. drug product development.

Read the full article here