A Fundamental Study on Compression Properties and Strain Rate Sensitivity of Spray-Dried Amorphous Solid Dispersions.

Amorphous solid dispersions (ASDs) are a proven method of improving the solubility and bioavailability of poorly soluble compounds. Immediate release tablets are frequently used as final dosage form for ASDs. Increasing tableting process throughput during clinical development requires using larger, faster tablet presses which subject materials to higher strain rate. Many pharmaceutical materials show strain rate sensitivity, i.e., yield pressure sensitivity to compression speed. Currently, there is only scattered information available in scientific literature on how ASDs behave under different tablet compression speeds. The purpose of this study was to examine spray-dried ASDs' sensitivity to strain rate under compression in a comprehensive study. We also investigated the drivers for such a strain sensitive behavior. A set of sample spray-dried powders, selected for their range of properties, were compressed using a simulated Korsch XL100 profile at 3 and 30 RPM and V-profile at 0.1 and 300 mm/s on a Phoenix compaction simulator. The sample set included samples with varying API content (0-50% w/w), stabilizing polymer (HPMC, HPMC-AS, PVP-VA), particle size, and bulk densities, produced on spray driers from lab to commercial scale. We identified that all ASD samples showed plastic flow and deformation behavior and form robust compacts at slow compression speeds. At high speed, tablet defects occurred. The strain rate sensitivity observed in this study was comparable or slightly superior to that observed for microcrystalline cellulose, known to be a mildly strain rate-sensitive material. We showed that compression speed is a critical process parameter for ASD-containing tablets.