Guiding excipient selection for amorphous solid dispersions by combining an in vitro-in-silico approach – II: Supersaturation and drug release

Abstract

There is a growing industrial need for quick and early screening of amorphous solid dispersions (ASDs). While new technologies are emerging, including in-silico predictions and high-throughput experimentation, a significant gap exists due to a lack of comparative data. The aim of this work was thus to compare experimental data with calculations obtained by the Conductor like Screening Model for Real Solvents (COSMO-RS). A small-scale high throughput method based on solvent casting was used to evaluate the release behavior and precipitation inhibition capacity of ASDs of griseofulvin and nifedipine in the presence of ten pharmaceutically relevant polymers. COSMO-RS was then used to investigate the interaction strength between drug and polymer by means of drug activity coefficients. A stronger interaction would result in better supersaturation maintenance. This was reflected in our results and a good alignment between calculations and experimental performance was observed. COSMO-RS effectively differentiated between polymers with strong precipitation inhibition (PI) functionality and separated those with weaker efficacy for most of the ASDs studied. This pre-selected list of polymers can serve as a foundation for additional studies on all relevant drug development quality attributes, from stability to manufacturing.