Improving Oral Bioavailability of Poorly Water-Soluble Drugs: Recent Progress in Solid Dispersions, Lipid Systems, and Nanotechnology

Abstract

Poor aqueous solubility remains one of the most significant challenges in pharmaceutical development, affecting approximately 40% of marketed drugs and 70–90% of developmental candidates. This constraint translates directly into inadequate oral bioavailability, reduced therapeutic efficacy, high inter- and intra-subject variability, and compromised dose proportionality. The Biopharmaceutical Classification System (BCS) characterises drugs with low solubility and high permeability (Class II) and those with both low solubility and permeability (Class IV) as particularly problematic for conventional oral formulation. Over the past two decades, three primary technological paradigms have emerged to address this challenge: solid dispersions, lipid-based formulations, and nanotechnology-enabled delivery systems. This review synthesises recent advances (2022–2025) across these platforms, examining their mechanistic basis, formulation strategies, in vivo performance, and regulatory landscape. We demonstrate that hybrid approaches combining multiple technologies now routinely achieve 3–7-fold improvements in oral bioavailability and are increasingly entering clinical practice