Solubilization of Poorly Water Soluble Drug Using Mixed Solvency Approach for Aqueous Injection

Aim: 1) To increase water solubility of indomethacin drug using mixed solvency approach.
2) To employ use of non toxic solubilizers for increasing solubility of a poorly water soluble drug.
Study Design: Trial and error based experimental study.
Place and Duration of Study: School of Pharmacy, Devi Ahilya Vishwavidyalaya, UTD, Takshashila Campus, Indore, India and College of Pharmacy, IPS Academy, Indore, India between Jan. 2011 and June. 2012.
Methodology: By making mixed solvent (40%) blends of selected water soluble substances from the hydrotropes (urea, sodium benzoate, sodium citrate, nicotinamide); water-soluble solids (PEG- 4000, PEG-6000); and co-solvents (propylene glycol, glycerine, PEG-200, PEG-400, PEG 600) solubility studies were performed with indomethacin (model drug). On the basis of solubility studies formulation was developed. The solubilized drug and prepared formulation were characterized by ultraviolet and infrared techniques. Various properties of solution such as pH, viscosity, specific gravity and surface tension were studied. The developed formulation was studied for physical and chemical stability.
Result: Aqueous solubility of drug in case of selected blends ranged from 14.55 mg/ml – 19.96 mg/ml (as compared to the solubility in distilled water 0.0464 ± 0.007 mg/ml). The enhancement in the solubility of drug in a mixed solvent containing 10% sodium benzoate, 5% sodium citrate and 25 % S cosolvent (25% S cosolvent contains PEG200, PEG 400, PEG600, Glycerine and Propylene glycol) was more than 400 fold. Prepared formulation F10 show appreciable physical and chemical stability.
Conclusion: The results of this study provide guidance for developing an injectable product and strategies for improving solubility as well as stability of poorly water soluble drug using the concept of mixed solvency. The proposed technique is economical, convenient and safe. The application of mixed solvency approach in the development of formulations shall prove a boon for pharmaceutical industries.