Miniaturized screening of polymers for amorphous drug stabilization (SPADS): rapid assessment of solid dispersion systems.

ABSTRACT

PURPOSE: Development of a novel, rapid, miniaturized approach to identify amorphous solid dispersions with maximum supersaturation and solid state stability. METHOD: Three different miniaturized assays are combined in a 2-step decision process to assess the supersaturation potential and drug-polymer miscibility and stability of amorphous compositions. Step 1 SPADS dissolution assay. Drug dissolution is determined in 96-well plates to detect systems that generate and maintain supersaturation. Promising combinations graduate to step 2. Step 2 SPADS interaction and SPADS imaging assays. FTIR microspectroscopy is used to study intermolecular interactions. Atomic force microscopy is applied to analyze molecular homogeneity and stability. Based on the screening results, selected drug-polymer combinations were also prepared by spray-drying and characterized by classical dissolution tests and a 6-month physical stability study. RESULTS: From the 7 different polymers and 4 drug loads tested, EUDRAGIT E PO at a drug load of 20% performed best for the model drug CETP(2). The classical dissolution and stability tests confirmed the results from the miniaturized assays. CONCLUSION: The results demonstrate that the SPADS approach is a useful de-risking tool allowing the rapid, rational, time- and cost-effective identification of polymers and drug loads with appropriate dual function in supersaturation performance and amorphous drug stabilization.