PermeaLoop™, a novel in vitro tool for small-scale drug-dissolution/permeation studies

Abstract

Here we report first experiences with the novel in vitro dissolution/permeation setup PermeaLoop™. It was designed to overcome current limitations of in vivo predictive dissolution testing of enabling formulations, such as lack of relevant absorptive drag to allow for meaningful interplay between dissolution and permeation, as it is occurring in vivo. We propose a novel setup with a high area-to-volume ratio and report as a model case the dissolution/permeation behavior of an enabling formulation of the poorly soluble and poorly permeable drug ABT-869. Mini tablets consisting of an amorphous solid dispersion were tested at a downscaled clinically relevant dose. At room temperature, release was fast, and more than 35% of the employed dose permeated within 6 h. In consequence, the amount in the donor decreased significantly. By contrast, only 9% of the employed dose was released when performing the experiment at 35 °C. Still, most of the released drug permeated into the acceptor (>80%), and the permeation rate was release-dependent and vice versa, i.e. the scenario was highly dynamic. Hence, due to a sufficiently large permeation area the dissolution step became rate-limiting. Therefore, PermeaLoop™ is regarded a promising tool for evaluating enabling formulations.

Keywords: ABT-869; Amorphous solid dispersion; Dissolution; Dynamic; Non-sink; Non-steady state; Permeation.