PriMera Scientific Surgical Research and Practice (ISSN: 2836-0028)

Review Article

Volume 7 Issue 3

Strategies for Improving Solubility and Dissolution of Poorly Water-Soluble Drugs: Current Developments and Pharmaceutical Applications

K Chandramohan, R Nepolean, K Karthikeyan*, D Anbarasu and N Jayaram

March 02, 2026

DOI : 10.56831/PSSRP-07-248

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Abstract

Poor aqueous solubility is a significant hurdle in the development of Biopharmaceutics Classification System (BCS) Class 2 and 4 candidates, which often leads to poor dissolution, poor gastrointestinal absorption and poor oral bioavailability. This review makes an effort to examine in detail the inherent and extrinsic factors that affects solubility, taking consideration of such aspects as molecular architecture, crystalline lattice enthalpy, ionisation behaviour, hydrogen bonding potential, the pH gradient through the gastrointestinal tract and the occurrence of endogenous surfactants as well as the complexities of the supersaturation permeability interplay. Conventional strategies based on particle size reduction, pH regulation, salt formation, co-solvent system, solubilization mediated by surfactants and complexation of cyclodextrins provide foundation that is often found to have limitations in terms of physicochemical stability, limitations related to scaleup and precipitation phenomena in case of dilution. Recent advances in nanotechnology and materials science have introduced high efficacious strategies, represented by amorphous solid dispersions, nanocrystals, polymeric and lipid based carriers along with mesoporous carriers and supercritical fluid processing. Emerging platforms, especially co-amorphous formulations, deep eutectic solvents, ionic liquids, hybrid nanostructures and 3D printing of dosage units increases solubility and bioavailability even more. Collectively, these innovations supported by AI enabled predictive modeling are promising giants toward the realization of strong patient centric solutions for poorly water soluble therapeutics.

Keywords: Solubility enhancement; Amorphous solid dispersions; Nanotechnology; Lipid based drug delivery; Poorly water soluble drugs

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