Water-Induced Phase Separation of Spray-Dried Amorphous Solid Dispersions
Na Li, Jonathan L. Cape, Bharat R. Mankani, Dmitry Zemlyanov, Kimberly B. Shepard, Michael M. Morgen, Lynne S. Taylor
Abstract
O/MeOH solvent mixture showed phase heterogeneity with all analytical methods used. The surface composition of dispersion particles as measured by fluorescence spectroscopy and XPS showed good agreement, suggesting surface drug enrichment of the spray-dried ASD particles prepared from this solvent system. Calculated phase diagrams and drying trajectories were consistent with experimental observations, suggesting that small variations in solvent composition may cause significant changes in ASD phase behavior during drying. These findings should aid in spray-drying process development for ASD manufacturing and can be applied broadly to assess the risk of phase separation for spray-drying systems using mixed organic solvents or other solvent-based processes.