(281a) Generation of Amorphous Solid Dispersions through Co-Precipitation for Enhanced Physical Properties

Due to the increasing number of new chemical entities that exhibit poor solubility, various strategies have been applied to improve the bioavailability, such as amorphous solid dispersions, salts/cocrystal formation, complexation techniques, lipid-based delivery systems, nanoscale drug delivery systems and particle size reduction. Converting the crystalline APIs into amorphous solid dispersions (ASDs) is gaining particular interest as it helps scientists address the challenges associated with poor drug solubility and ultimate leading to improved therapeutic outcomes.

ASDs often employ a polymer matrix to disperse the drug, which stabilize the amorphous state, preventing drug recrystallization. The amorphous state of the drug in ASDs can achieve higher apparent solubility, facilitate drug dissolution, and improve bioavailability. The common methods to prepare amorphous solid dispersions including spray drying and hot melt extrusions. The choice of the method depends on various factors including the drug and polymer properties, formulation requirements, and scale of production. Although ASDs offer numerous advantages, controlling physical properties of the resulting ASDs, such as the morphology, particle size distribution, density, and flowability, can be sometimes very challenging.

Herein, we developed a co-precipitation strategy to generate ASDs with well controlled morphology, uniform particle size distribution, high bulk density, and good flowability. The resulting materials were directly compressed into an oral tablet. The dissolution performance was compared against the spray dried dispersions (SDDs). In vivo results suggest the tablets can achieve equivalent pharmacokinetic performance.