Hydrotropy: A Promising Solubilization Technique for Poorly Water-Soluble Drugs

Abstract

The low aqueous solubility has continued to be one of the greatest challenges in the current pharmaceutical sciences since a great percentage of the emerging therapeutic molecules are characterized by low water solubility and dissolution-limited absorption. Drugs that fall under Biopharmaceutics Classification System (BCS) Class II and IV are often characterized by poor dissolution properties, unpredictable oral bioavailability, slow absorption and unpredictable therapeutic effects. Traditional methods of solubility enhancement like micronization, salt formation, co-solvency, surfactant system, cyclodextrin complexation, solid dispersions and nanotechnology-based methods have demonstrated a lot of success but are also accompanied by some limitations like toxicity, solvent contamination, high cost of production, physical instability and complicated scale-up processes. Hydrotropy has become a cost-effective, environmentally friendly, and industrially viable alternative to enhance aqueous solubility of poorly water-soluble drugs. Hydrotropic agents, including sodium benzoate, sodium salicylate, sodium citrate, nicotinamide, and urea, enhance solubility and increase the wettability via self-aggregation, hydrogen bonding, π–π interactions, solvent structure alteration, and solubility enhancement. Recent developments in mixed hydrotropy also enhanced pharmaceutical applications by decreasing toxicity, and augmenting synergistic solubilization effects. Hydrotropic systems have proved to be widely applicable in oral, parenteral, topical, transdermal, ocular and analytical preparations. This review critically discusses the historical background, mechanisms, classifications, pharmaceutical applications, advantages, limitations, comparative evaluation, and future perspectives of hydrotropic solubilization. Mixed hydrotropy and green pharmaceutical manufacturing have been given a special focus.

Keywords: Hydrotropy, mixed hydrotropy, poorly water-soluble drugs, solubilization enhancement, bioavailability, hydrotropic agents, pharmaceutical formulation