Development of Parenteral Formulation of Poorly Water Soluble Drugs: The Role of Novel Mixed-solvency Concept

Abstract

Context: Water solubility is an important molecular property for successful drug development as it is a key factor governing drug access to biological membranes. The solubilization of poorly water soluble drug by facilitated mixed solvency is presented. Aim: The aim was to develop the injection formulations of the model poorly water-soluble drug. Settings and Design: Trial and error based experimental study. Materials and Methods: Mixed solvency approach was used to solubilize the hydrophobic drug. Mixed solvent system prepared using water-soluble hydrotropes (such as sodium citrate and urea) and water-miscible cosolvents, such as polyethylene glycol (PEG) 200, PEG 300, PEG 400, PEG 600, glycerin, propylene glycol, and ethanol. Drug was characterized using ultraviolet, Fourier Transform infrared (FT-IR), and Raman spectroscopy. Solubilizing power (Φ) and the Gibbs free energy of transfer (ΔG0tr) were determined. Various properties of solution such as pH, viscosity, specific gravity, and refractive index were also studied. Results: Desired solubility of drug achieved in a mixed solvent blend AF5, which was more than 200 fold as compared to the solubility in distilled water 0.152 mg/ml. Drug content was found to be more than 98%. FT-IR and Raman spectroscopy results may support intermolecular hydrogen bonding between drug and mixed solvent system. Developed formulation was physically and chemically stable. Conclusion: This technique proved a synergistic enhancement in solubility of a poorly water soluble drug due to mixed solvent effect and produces a stable formulation. Mixed solvency concept may reduce the individual concentration of solubilizers and so reduce their toxicity associated with them.