Formulating poorly water-soluble compounds as amorphous solid dispersions (ASDs) is one of the most promising approaches to enhance solubility and/or dissolution, and membrane flux to improve bioavailability. Due to the unstable nature of amorphous materials and the underlying principle for their formation, it is clear that the manufacturing technology and process conditions would impact ASD material characteristics and properties, and in turn in vivo performance. The purpose of this work is to evaluate the interrelationship of microstructure, properties, and dissolution performance for ASDs prepared using spray drying and co-precipitation via resonant acoustic mixing. We applied both conventional characterization tools and X-Ray Microscopy (XRM) to assess the contribution of microstructure to the characteristics of ASDs and obtain additional quantification and understanding of the drug product intermediates and tablets. The results showed strong interrelationship of microstructure, particulate and bulk powder properties, and dissolution performance for ASDs. XRM image-based analysis is a powerful tool to assess the contribution of microstructure to the characteristics of ASDs and provide mechanistic understanding of the interrelationship.
Helen Hou, Principal Scientist, Small Molecule Pharmaceutical Sciences, Genentech