Recent Advances in Formulation Approaches to Enable Oral Delivery of Poorly Water-Soluble Drugs

Poorly water-soluble drugs remain a major challenge in oral drug development. Amorphous solid dispersions (ASDs) and lipid-based formulations (LBFs) are the two most widely used enabling technologies, each improving bioavailability by generating and maintaining intestinal supersaturation. Although they use different formulation approaches, both aim to keep drugs in a non-crystalline, molecularly dispersed state and rely on amorphous drug-rich nanodroplets to support absorption. Increasingly, ASD and LBF strategies are converging through the incorporation of surfactants, polymers, and hybrid technologies. Formulation selection depends on physicochemical properties, manufacturing considerations, and development needs. Emerging beyond-rule-of-5 molecules will require advanced hybrid approaches addressing both solubility and permeability limitations.