Assessing the performance of amorphous solid dispersions

The characterization and performance of stable amorphous solid dispersion systems were evaluated in 40 research papers reporting active pharmaceutical ingredient (API) dissolution and bioavailability from various systems containing polymers. The results from these studies were broadly placed into three categories: amorphous dispersions that improved bioavailability (similar to 82% of the cases), amorphous dispersions possessing lower bioavailability than the reference material (similar to 8% of the cases), and amorphous dispersions demonstrating similar bioavailabilities as the reference material (similar to 10% of the cases). A comparative analysis of these studies revealed several in vitro and in vivo variables that could have influenced the results. The in vitro factors compared primarily centered on dissolution testing and equipment, content and amount of dissolution media, sink or nonsink conditions, agitation rates, media pH, dissolution characteristics of the polymer, and dispersion particle size. The in vivo factors included reference materials used for bioavailability comparisons, animal species utilized, fasting versus fed conditions, and regional differences in gastrointestinal (GI) content and volume. On the basis of these considerations, a number of recommendations were made on issues ranging from the assessment of physical stability of APIpolymer dispersions to in vivo GI physiological factors that require consideration in the performance evaluation of these systems. (c) 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:13551377, 2012