Dissolution Model Development: Formulation Effects and Filter Complications

Abstract

This study describes various complications related to sample preparation (filtration) during development of a dissolution method intended to discriminate among different fenofibrate immediate-release formulations. Several dissolution apparatus and sample preparation techniques were tested. The flow-through cell apparatus (USP 4) was found unfit for dissolution testing of fenofibrate MeltDose formulations due to clogging of filters and varying flow rates. A mini paddle dissolution setup produced dissolution profiles of the tested formulations that correlated well with clinical data. The work towards the mini paddle dissolution method demonstrates that sample preparation influenced the results. The investigations show that excipients from the formulations directly affected the drug–filter interaction, thereby affecting the dissolution profiles and the ability to predict the in vivo data. With the tested drug–formulation combination, the best in vivo–in vitro correlation was found after filtration of the dissolution samples through 0.45-μm hydrophobic PTFE membrane filters.