Oral bioavailability

The oral bioavailability of many medications, especially BCS Class II and Class IV substances, is significantly limited by poor water solubility. Three main options for improving bioavailability are examined in this review: solid dispersions, lipid-based drug delivery systems, and nanotechnology-based methods. Lipid-based systems like SEDDS, SMEDDS, and SNEDDS promote solubilisation and absorption, whereas solid dispersions improve drug dissolution by amorphization and improved wettability. By increasing surface area and improving permeability, nanotechnology-based carriers—such as nanoparticles, nanosuspensions, and nanoemulsions—further boost drug delivery. These technologies considerably increase oral bioavailability, solubility, and dissolution rate, according to the reviewed research. Stability, scalability, production, and regulatory approval are still issues, though. Promising prospects for future developments in oral medication delivery are provided by cutting-edge techniques, including hybrid delivery systems and formulation design aided by artificial intelligence.

Poor aqueous solubility is a major limitation in pharmaceutical development, affecting nearly 40% of approved drugs and up to 90% of drug candidates in the discovery pipeline. Low solubility directly compromises oral bioavailability, therapeutic effectiveness, dose proportionality, and clinical reproducibility, particularly for drugs classified under Biopharmaceutical Classification System (BCS) Classes II and IV. To address these challenges, formulation science has advanced significantly over the past two decades. This review critically evaluates recent progress from 2022 to 2025 in three major technological approaches: solid dispersions, lipid-based formulations, and nanotechnology-enabled drug delivery systems. Emphasis is placed on mechanistic principles governing solubility enhancement, formulation design strategies, in vivo performance outcomes, and translational considerations. Emerging hybrid platforms that integrate polymers, lipids, and nanocarriers are also discussed, as they demonstrate synergistic improvements in dissolution rate, permeability, and systemic exposure, often achieving 3–7 fold enhancement in oral bioavailability. In addition, the evolving regulatory landscape for complex and nanotechnology-based formulations is examined, highlighting current expectations for characterization, stability, and safety evaluation. Overall, this review provides an updated and integrated perspective on formulation strategies for poorly soluble drugs, offering practical insights for both academic research and industrial development.