Experimental Advances in Drug Solubility and AI-Driven Strategies for Drug Solubility Enhancement: Current Trends and Future Prospects

The aqueous solubility of a drug is a fundamental determinant of its therapeutic efficacy, directly influencing dissolution rates, absorption, and systemic bioavailability. Currently, a significant portion of new drug candidates face challenges related to poor aqueous solubility, particularly those within Biopharmaceutical Classification System classes II and IV. This review explores the latest advancements in both traditional and AI-driven methodologies for enhancing drug solubility, critically examining their mechanisms, applications, and impact on drug development. The current published literature was exhaustively explored and gathered from reliable sources. Results from the literature search revealed that physical techniques like micronization and others increase the contact surface area to enhance solubility, which has been shown to increase the dissolution of poorly aqueous soluble drugs. Beyond traditional methods, the scope of emerging technologies, such as 3D printing for customized formulations, co-amorphous systems, and the integration of artificial intelligence in formulation development, has also been reported. Furthermore, this review emphasises that selecting the optimal solubility enhancement strategy is essential for achieving objectives like reduced dose frequency, improved patient compliance, and maintaining low production costs. By systematically analyzing the advantages and limitations of diverse methodologies, this review will guide researchers and formulation scientists in developing successful pharmaceutical products for poorly water-soluble drug candidates.