Designer excipients enable oral delivery of poorly soluble drugs

Upon oral administration of active pharmaceutical ingredients, achieving adequate absorption for therapeutic effect remains a key challenge for the majority of pipeline drug candidates.¹ This is attributed to poor water solubility of hydrophobic and often crystalline small drug molecules. Amorphous solid dispersions (ASDs) have emerged as viable nanomaterials to overcome intrinsic solubility limitations by supersaturating the drug in solution.² However, preventing reprecipitation over pharmaceutically-relevant time scales mandates nanocarriers that can effectively stabilize amorphized drug molecules. Here, we employ a directed design approach to build libraries of tailored polymers as ASD excipients around the chemical structures of antiseizure and antiandrogen drugs, phenytoin and nilutamide, respectively. High-throughput synthesis and screening tools aided in the development of robust controlled delivery systems that maintained elevated drug concentrations and enhanced oral bioavailability metrics above reported studies to date.³.