Comparative Assessment of Miniaturized Screening Approaches for Selection of Polymers for Amorphous Drug Stabilization.

The present work highlights the use of miniaturized approaches to screen and prioritize development of solid dispersions that provide stabilization of the amorphous drug against crystallization and enhanced dissolution over the crystalline form. The approaches evaluated include solvent casting and solvent displacement-based techniques. Four compounds were evaluated with both these screening approaches. A dual-pH dilution method using fasted state simulated gastric fluid and fasted state simulated intestinal fluid as media was used to evaluate solubility enhancement ratio in each well of the screen. The concentration at 15 mins after dilution with fasted state simulated intestinal fluid and super-saturation ratio at the end of the dissolution study is used as 2 descriptors of solubility enhancement. The empirical screening approaches were supplemented with theoretical calculations of solubility enhancement to gauge the best-performing amorphous solid dispersion (ASD). Physical stability of the amorphous systems was also evaluated, where applicable. Lead ASD compositions from the screens were scaled up to verify the predictions. To our knowledge, this is the first report where the 2 most common screening approaches for the development of ASDs are compared head to head. These approaches are rapid, material sparing, and can be adapted to accommodate screening of multiple variables such as polymer type, drug load, and ternary systems simultaneously. The strengths, limitations, and most suitable applications for each of the 2 methods are also discussed.