Design of a Re-Dispersible High Drug Load Amorphous Formulation

Amorphous solid dispersions (ASD) are a commonly used enabling formulation technology to drive oral absorption of poorly soluble drugs. To ensure adequate solid-state stability and dissolution characteristics, the ASD formulation design typically has ≤ 25% drug loading. Exposed to aqueous media, ASD formulations can produce drug-rich colloidal dispersion with particle size < 500 nm. This in situ formation of colloidal particles requires incorporation of excess excipients in the formulation. The concept of using engineered drug-rich particles having comparable size as those generated by ASDs in aqueous media is explored with the goal of increasing drug loading in the solid dosage form. Utilizing ABT-530 as model compound, a controlled solvent-antisolvent precipitation method resulted in a dilute suspension that contained drug-rich (90% (w/w)) amorphous nanoparticles (ANP). The precipitation process was optimized to yield a suspension containing < 300 nm ANP. A systematic evaluation of formulation properties and process variables resulted in the generation of dry powders composed of 1-8 µm agglomerates of nanoparticles which in contact with water regenerated the colloidal suspension having particle size comparable to primary particles. Thus, this work demonstrates an approach to designing a re-dispersible ANP based powder containing ≥90% w/w ABT-530 that could be used in preparation of a high drug load solid dosage form.