Relationships between solid dispersion preparation process, particle size and drug release – An NMR and NMR microimaging study

Abstract

Solid dispersion tablets prepared by either spray drying or rotoevaporation and exhibiting different grain and pore sizes were investigated under the process of hydration-swelling-gelation. 2H and 1H NMR microimaging experiments were used to selectively follow water penetration and polymer mobilization kinetics, respectively, while the drug release kinetics was followed by 1H NMR spectroscopy. The obtained data, in combination with morphological information by scanning electron microscopy (SEM), reveal a complex process that ultimately leads to release of the drug into the aqueous phase. We find that the rate of water ingress has no direct influence on release kinetics, which also renders air in the tablets a secondary factor. On the other hand, drug release is directly correlated with the polymer mobilization kinetics. Water diffusion into the originally dry polymer grains determines the rate of grain swelling and the hydration within the grains varies strongly with grain size. We propose that this sets the stage for creating homogeneous gels for small grain sizes and heterogeneous gels for large grain sizes. Fast diffusion through water-rich sections of the inhomogeneous gels that exhibit a large mesh size is the factor which yields a faster drug release from tablets prepared by rotoevaporation.