FORMULATION DEVELOPMENT OF AQUEOUS INJECTION OF POORLY SOLUBLE DRUG USING MIXED HYDROTROPIC SOLUBILIZATION CONCEPT AND ITS EVALUATION
Abstract
Furosemide is a high ceiling diuretic that exhibits antihypertensive activity and also used in treatment of edema associated with congestive heart failure, liver cirrhosis, renal disease, including nephrotic syndrome. It is practically insoluble in water. The effect of hydrotropes such as urea, sodium citrate, sodium benzoate, sodium acetate and blends on the solubility of furosemide was investigated. The enhancement in the solubility of furosemide was up to 200.46 fold in 40% sodium benzoate solution, 14.81 fold in 40% urea solution, 11.85 fold in 40% sodium citrate solution and 9.35 fold in 40% sodium acetate solution compared to its solubility in distilled water. The solubility of drug was raised up to 357.87 fold in blend BUC (containing sodium benzoate, urea and sodium citrate in the ratio of 13.3:13.3:13.3) which was about 1.35 times more than the solubility in the blend BU (containing sodium benzoate and urea in the ratio of 20:20). This proved a synergistic enhancement in solubility of a poorly water soluble drug due to mixed hydrotropy. Combination of hydrotropic agents giving synergistic solvent action can minimize the amount of hydrotropic agents employed, minimizing the chances of their individual toxicities. Aqueous injection of furosemide, using the mixed hydrotropic solubilization technique, was developed. The developed formulation was studied for physical and chemical stability. The prepared formulation was unaffected in respect of color stability. There was no color change or precipitate was found in the developed formulation. In the freeze thaw study there was no precipitation and no turbidity in the developed parenteral formulation at the end of the testing. Chemical stability showed that there was no appreciable loss of furosemide in the formulation stored for 30 days at different temperatures. So it can be assumed that the formulation will have sufficient chemical stability at room temperature.
Keywords:
Mixed hydrotropy, solubilization, furosemide, aqueous injection, urea, sodium acetate, sodium benzoate, synergistic enhancementDOI
https://doi.org/10.25004/IJPSDR.2015.070102References
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