Novel Dissolution Approach for Tacrolimus-Loaded Microspheres Using a Dialysis Membrane for <i>in Vitro</i>–<i>in Vivo</i> Correlation

Abstract

The aim of this study was to establish a novel approach to in vitro dissolution evaluation using a combination of the paddle method and a dialysis membrane, both to predict the overall in vivo performance of tacrolimus microspheres and also to identify a suitable dissolution test method to describe the in vivo initial burst phenomenon. This new dissolution method for evaluating the release of tacrolimus from microspheres consisted of rotating a customized paddle inside a dialysis membrane using a conventional paddle apparatus. Findings were compared with a method in which the paddle was rotated outside the dialysis membrane, the conventional paddle method, and the flow-through cell method. We concluded that the paddle method with a dialysis membrane and internal agitation, which was designed to mimic in vivo conditions, predicted the overall pharmacokinetic (PK) profile of tacrolimus microspheres whereas the conventional paddle method described the initial burst. These findings suggest that it may not be possible to predict both the PK profile and initial burst using a single analysis method. We therefore recommend that evaluation of the initial burst be performed separately. In conclusion, we propose that combination of the paddle method with a dialysis membrane and internal agitation to evaluate the overall PK profile, together with the paddle method to describe the in vivo initial burst, represents a novel approach to in vitro dissolution evaluation for microsphere formulations.

Recent Progress in Drug Release Testing Methods of Biopolymeric Particulate System

“…Recently, Park et al reported good IVIVC of PLGA microparticles containing norquetiapine ( N -desalkyl quetiapine), which is an active metabolite of quetiapine, where point-to-point relationship of r 2 greater than 0.98 between in vitro release (SS method) and in vivo release in rats was obtained [ 110 ]. Recently, Kaihara et al developed an in vitro release testing method by rotating a customized paddle inside a dialysis membrane to predict the in vivo drug release properties of tacrolimus-loaded microparticles [ 111 ]. This study found that it may not be possible to predict both the overall drug release profile and the initial burst using a single method.…”