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

Abstract

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 distribution of liquid within fully liquid penetrated beads. These techniques were used to rationalise the increase in the drug release rate with increasing proportion of GMS (glycomonosaccharide):paraffin in the matrix composition. 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 showed the same trend with increasing GMS content as the rate of drug release. The total concentration of absorbed liquid increased and its T2 relaxation time decreased with increasing GMS content of the bead matrix. This combined 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 in liquid distribution within the beads were quantified using percolation analysis and were related to the lipid matrix composition and may be a contributory factor in determining the rate of drug release.