Development of a dissolution test for extended-release bromopride pellets with in vivo–in vitro correlation

Abstract

The aim of this study was the development of a dissolution test with IVIVC for extended-release bromopride (BPD) pellets using bioavailability data. BPD is a Biopharmaceutics Classification System Class 2 drug, and its absorption is primarily limited by its dissolution rate. Despite this, there are no reports describing a dissolution test for BPD dosage forms. The dissolution medium was selected based upon the sink condition and the gastrointestinal pH. Furthermore, USP Apparatus 1 and 3 were tested, and the dissolution method was compared with that outlined by the manufacturer of the reference drug. Deconvolution by the Wagner–Nelson method was used to obtain the fraction of drug absorbed. The dissolution test that yielded IVIVC for both the fasted and fed states (R2 > 0.97) and also the discriminative power used Apparatus 1 at 75 rpm in 900 mL of HCl. The dissolution medium (900 mL PBS pH 7.2) was changed after 1 h. Additionally, quantitative analysis was successfully validated by UV absorption (273 nm). Drug release is controlled by the pellet coating and by BPD solubility. The Higuchi release kinetics model best describes the dissolution of commercial BPD pellets batches.