The purpose of this evaluation was to enhance the solubility and bioavailability of poorly soluble medications through a variety of methods such as physical, chemical, and other modifications or techniques. Solubility refers to the maximum amount of solute that can dissolve in a specific amount of solvent or solution at a given temperature. Achieving the desired concentration of a drug in systemic circulation is crucial for the pharmacological response to be effective. Poor aqueous solubility can significantly impact drug efficacy and may lead to side effects. Various techniques are employed to improve aqueous solubility, which can ultimately enhance efficiency and reduce side effects for certain drugs. These techniques are applicable to parenteral, topical, and oral solutions. Physical modification techniques such as media milling/nanocrystal technology, cryogenic technology, supercritical fluid processes, crystal habit modification, complexation, micellar technologies, chemical modifications, and other methods like co-crystallization, co-solvency, and hydrotrophy are utilized to enhance the solubility of highly soluble drugs such as dolargin, loperamide, tubocurarine, doxorubicin, ibuprofen, griseofulvin, diazepam, naproxen, carbamazepine, nifedipine, and phytosterol.