SOLUBILITY ENHANCEMENT AND ANALYTICAL TECHNIQUES: A COMPREHENSIVE REVIEW ON IMPROVING BIOAVAILABILITY OF POORLY SOLUBLE DRUGS WITH EMPHASIS ON HPLC

Aqueous solubility refers to a drug’s ability to dissolve in water or an aqueous medium, and this property plays a pivotal role in determining its effectiveness. A major challenge in modern drug development is that a large proportion around 70–90% of investigational compounds and approximately 40% of marketed drugs exhibit low solubility. This limitation often results in insufficient absorption, compromised therapeutic action, and the need for higher dosages. To address this, a variety of physical and chemical strategies have been explored, such as reducing particle size, formulating solid dispersions, employing supercritical fluids, using cryogenic processing, and developing inclusion complexes. Other advanced approaches include the use of prodrugs, salt forms, co-crystals, co-solvents, hydrotropes, and pH-based solubility modulation. Additionally, nanotechnology-based systems like liposomes, micelles, dendrimers, nanogels, and nanosuspension have shown promise in enhancing drug solubility. Despite these advances, no universal solution exists, highlighting the ongoing need for simplified and scalable techniques that can broaden commercial applicability.