This paper describes broadly applicable formulation approaches and biomodeling tools that have been successfully used to improve the solubility and in vivo performance of low-solubility compounds—an increasingly larger component of compounds within pharmaceutical industry pipelines. The approaches, including spray-dried drug/polymer dispersions and drug/polymer nanoparticles, are ideally suited for use early in the drug-development process from discovery through formulation and toxicology screening. The approaches are readily scalable, facilitating progression of compounds through commercial manufacture.