Real-Time in Vitro Drug Dissolution Studies of Tablets Using Volume-Localized NMR (MRS)

Abstract

An approach to measure in vitro drug dissolution rates employing spatially resolved nuclear magnetic resonance (NMR) is reported, as a complement to standard United States Pharmacopeia protocols. Measurements are performed under conditions that mimic the physiological (pH 1, temperature 37° C). In order to register realistic dissolution rates, the sample is stirred in the magnetic field, employing a setup that is described. While the stirrer in the sample cell does degrade spectral resolution even in volume-localized mode, it proves possible nevertheless to acquire ‘high resolution’ information. Measurements are performed employing ‘point resolved spectroscopy’ (PRESS) by tracking drug concentration in a selected voxel in the dissolution medium as a function of time. The dissolution of the tablets in vitro follows first-order kinetics under the non-sink conditions of these experiments, the measured rate constants reflecting characteristic differences in dissolution rates of different formulations. We supplement this study with diffusion-weighted imaging of water ingress into the tablets, confirming the trends.