A Novel Architecture for High Drug-loaded Amorphous Solid Dispersion Tablets; Assessment of in Vitro and in Vivo Performance, Stability and Manufacturability

Amorphous solid dispersions (ASDs) can increase solubility and dissolution rate of poorly water soluble drugs. However, ASD dosage forms are often large or require multiple units to meet dose requirements due to incorporation of concentration-sustaining polymers (CSPs) in the formulation. To address this challenge, a high-loaded dosage form (HLDF) architecture for ASDs was developed, in which a drug is first spray-dried with a high glass transition temperature (Tg) dispersion polymer to facilitate high drug loading while maintaining physical stability. The ASD is then granulated with a CSP to extend supersaturation in solution. The HLDF approach differs from traditional ASD architectures in which the dispersion polymer inside the ASD has the dual purpose of maintaining physical stability and extending supersaturation in solution, thereby constraining the formulation and often resulting in low dosage form drug loading. The HLDF platform has the potential to reduce tablet mass by at least 40% while maintaining performance, stability and manufacturability. This presentation describes case studies highlighting the HLDF architecture, including physical stability, in vitro and in vivo performance and manufacturability.