Controlled API-polymer solidification (CAPS): a novel manufacturing process approach to produce amorphous solid...

Increasing molecular size and lipophilicity of new chemical entities (NCEs) significantly decrease their aqueous solubility. It is estimated that 70 %+ of the NCEs in drug development pipelines are categorized as BCS class II or IV. Formulating a bioavailable drug is one of the toughest challenges Pharmaceutical Development is facing today. Amorphous solid dispersions (ASDs) prepared via hot-melt extrusion (HME) and spray drying are among the most commonly used strategies to enhance the solubility and bioavailability of poorly soluble compounds. However, despite these advancements, the material properties of ASDs continue to present formulation and processing challenges in drug product manufacturing. Herein, we introduce a novel Controlled API-Polymer Solidification (CAPS) technology for a cost-effective preparation of ASDs with superior physical properties, including improved density, flowability, and particle size distribution. These enhanced properties facilitate streamlined drug product manufacturing, enabling direct compression into tablets without additional processing steps. In-vitro dissolution and permeation studies, as well as in-vivo pharmacokinetic (PK) evaluations, demonstrated that CAPS-prepared ASDs exhibit bioequivalence to spray-dried formulations. This study highlights the advantages of CAPS as an alternative ASD manufacturing approach, offering enhanced physical properties and simplified downstream processing compared to conventional ASD strategies.