The expanding role of formulations to enable oral delivery of poorly water-soluble drugs

# The expanding role of formulations to enable oral delivery of poorly water-soluble drugs *Published: 2026 Apr 2* Contemporary small-molecule drug candidates increasingly have limited aqueous solubility, rendering oral delivery challenging. Amorphous solid dispersions (ASDs) and lipid-based formulations (LBFs) have evolved as leading formulation approaches to mitigate solubility and dissolution rate limitations. There is an increasing trend towards ASD formulations for drug candidates with high melting points and LBFs for extremely lipophilic molecules. Mechanistic assessment of LBF and ASD enhancement pathways reveals a surprising amount of commonality, notably that supersaturation generation and maintenance are likely key to obtaining optimized in vivo performance for both formulation types. An expanding formulation design space is blurring the distinction between these solubility enhancement technologies and further evolution in this direction is likely necessary to address the oral delivery of even more challenging molecules, such as proteolysis-targeting chimeras and macrocyclic peptides. DOI: 10.1038/s41573-026-01407-5