Hot melt extrusion (HME) to prepare amorphous solid dispersions (ASDs) at temperatures below the drug's melting point requires the crystalline drug to dissolve into the molten polymer. This requires an understanding of the drug's solubility in the molten polymer as well as amorphization (crystal dissolution) kinetics. The goal of this study was to identify drug crystal attributes which contribute to rapid amorphization during hot melt extrusion processing to form ASDs. Particle engineering approaches were used to recrystallize bicalutamide with different particle size distributions and defect density. These lots were then used to prepare ASDs by HME to monitor the amorphization kinetics. Particle size had the expected effect on the amorphization rate, and defect density was also observed to accelerate amorphization. A population balance model using dissolution and breakage phenomena was developed to investigate the dynamic evolution of crystal size distribution during a hot melt extrusion process, and parameter estimation was utilized to simulate the experimental HME results. Breakage kinetics were found to dominate the crystal dissolution process, synergistically accelerated by particles with high defect density. The findings have implications for particle engineering of crystals to enable the hot melt extrusion process, as well as improved process modeling through incorporating particle attributes.
Burnout, illness, and return in the twilightThis information is current as of November 12, 2018 Services Updated Information & http://n.neurology.org/content/91/20/934.full including high resolution figures, can be found at: Citations http://n.neurology.org/content/91/20/934.full##otherarticles This article has been cited by 1 HighWire-hosted articles: Subspecialty Collections http://n.neurology.org/cgi/collection/hematologic Hematologic http://n.neurology.org/cgi/collection/electronic_medical_records Electronic medical records http://n.neurology.org/cgi/collection/all_clinical_neurology All Clinical Neurology following collection(s):This article, along with others on similar topics, appears in the
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.