(37c) Impacts of Surface Composition on Dissolution Performance of Amorphous Solid Dispersions

Amorphous solid dispersion (ASD) plays a governing role in improving the bioavailability and solubility of poorly soluble drugs. Amorphous solid dispersions are a solid solution of drug, polymer and sometimes even surfactants. Depending on the phase behavior and miscibility of the components of ASD, process variations can sometimes lead to compositional differences on the surface. In this work, we study and understand how changes in surface concentration of ASD with same composition can impact their physical stability and dissolution behavior. Spraying drying technique is utilized in our experiments to generate ASD. We employ a formulation containing polyvinyl pyrrolidone vinyl acetate (PVP-VA), sodium lauryl sulfate (SLS) and drug. Surface concentration can be modified by varying the solvent systems and solid loading used in the spray drying process while maintaining the same ASD composition. Dissolution and accelerated physical stability of the resulting ASD were assessed and compared to a reference process. The ASD samples with different dissolution performance / physical stability were further evaluated for differences in surface concentration. We have thus confirmed that surface concentration of ASD can be influenced by process changes while preserving the identical ASD composition. We will explore the driving forces that lead to differences in surface concentration and gain fundamental insights into interplay of these mechanisms on the drug product performance.