Abstract: Poor solubility remains a significant obstacle in drug administration, adversely affecting the bioavailability and therapeutic efficacy of many drugs. It is also recognized as a primary factor contributing to issues with bioavailability, such as poor, inconsistent, limited, and highly variable bioavailability of marketed products. It is estimated that 40% of marketed drugs face bioavailability challenges primarily due to poor water solubility, and about 90% of pharmacological compounds exhibit poor water solubility in their early development stages. Addressing this issue is crucial for improving drug performance, efficacy, and patient outcomes. This review provides an overview of the challenges associated with poorly soluble drugs, including low bioavailability, limited dissolution rates, inconsistent absorption, decreased patient compliance, formulation difficulties, and associated costs and time constraints. Numerous strategies have been now investigated to tackle the issue of poor solubility. This review offers an updated overview of commonly used macro and nano drug delivery systems, including micelles, nanoemulsions, dendrimers, liposomes, lipid-based delivery systems, microemulsions, cosolvents, polymeric micelle preparation, drug nanocrystals, solid dispersion methods, crystal engineering techniques, and microneedle- based systems. Additionally, the review examines advanced techniques like cyclodextrin- based delivery systems, co-solvency and co-crystallization approaches, polymeric micelles, spray drying, co-precipitation, and amorphous solid dispersion. The role of computational modeling and formulation prediction is also addressed. Recent advancements in protein-based approaches, 3D printing, mesoporous silica nanoparticles, supramolecular delivery systems, magnetic nanoparticles, nanostructured lipid carriers, and lipid-based nanoparticles are highlighted as novel solutions for enhancing the solubility of poorly soluble drugs. The review concludes with predictions for the future, emphasizing the potential for further innovation in drug delivery methods to overcome the challenges associated with poorly soluble drugs.
Bakrey et al. (2025) studied this question.