NMR microscopy of the uptake, distribution and mobility of dissolution media in small, sub-millimetre drug delivery systems

NMR techniques were used to study the drug release process from small (sub- mm) lipophilic matrix theophylline beads. NMR microscopy was used to follow the ingress of the dissolution medium into the beads. Pulsed gradient spin echo (PGSE) NMR and 3D NMR imaging were used to measure the mobility and d istribution of liquid within fully liquid penetrated beads. These technique s were used to rationalise the increase in the drug release rate with incre asing proportion of GMS (glycomonosaccharide) :paraffin in the matrix compo sition. A well-defined penetrant front was seen to move towards the centre of the bead during the dissolution process and the rate of liquid uptake sh owed the same trend with increasing GMS content as the rate of drug release , The total concentration of absorbed liquid increased and its T-2 relaxati on time decreased with increasing FMS content of the bead matrix. This comb ined with the interpretation of PGSE results suggested that liquid resides in the matrix material as well as in pores left by the dissolved drug, and that this tendency increases with increasing GMS content. Heterogeneities i n liquid distribution within the beads were quantified using percolation an alysis and were related to the lipid matrix composition and may be a contri butory factor in determining the rate of drug release. (C) 2000 Elsevier Sc ience B.V. All rights reserved.