Amorphous Solid Dispersions as Enabling Formulations for Discovery and Early Development

摘要

It is frequently reported that the percentage of drug candidates that are limited by poor solubility is increasing [1,2]. These poorly soluble compounds typically require enabling formulations, and this trend creates challenges for teams in discovery and development who must drive in-vivo exposures high for animal toxicology studies and deliver robust dosageformsforclinical evaluation. Many enabling technologies are available for the formulator to consider, including lipids, cosolvents, surfactants, nanoparticles, cyclodextrin complexes, amorphous solid dispersions, and others. The suitability of the particular formulation approach depends largely on the physicochemical properties of the active pharmaceutical ingredient (API). Amorphous solid dispersions (ASDs) are particularly attractive for many poorly soluble drug candidates because these formulations offer many of the advantages of more conventional solid oral dosage forms but they also provide faster dissolution rates and higher drug concentrations in the gastrointestinal milieu [3]. Further, typical excipients utilized in production of ASDs are commercially available and they have proven to be well tolerated in vivo. We have successfully employed ASD technology to drive high plasma exposures in toxicology studies as well as to deliver challenging molecules in clinical studies. In this article we will discuss approaches for preparing, screening, characterizing, and dosing ASDs in preclinical and early development.