Novel application of hydrotropic solubilization in the analysis of some NSAIDs and their solid dosage forms

Abstract

Quantitative analysis of poorly water-soluble drugs involves use of various organic solvents. Major drawbacks of organic solvents include high cost, volatility and toxicity. Safety of analyzer is affected by toxicity of the solvent used. Sodium benzoate is one of the widely used hydrotropic agents and has demonstrated the enhancement in aqueous solubilities of a large number of poorly water-soluble drugs. In the present investigation 2 M sodium benzoate solution has been used as hydrotropic solubilizing agent for three poorly water-soluble, non-steroidal antiinflammatory drugs ibuprofen, flurbiprofen and naproxen. There were more than 80, 110 and 120 fold enhancements in the solubilities of ibuprofen, flurbiprofen and naproxen, respectively in 2 M sodium benzoate solution as compared to solubilities in distilled water. Therefore, 2 M sodium benzoate solution was employed to solubilize these drugs to carryout their titrimetric analyses. These drugs have been analyzed successfully in basic drug samples and in solid dosage forms. Proposed method is new, simple, economic, safe, rapid, accurate and reproducible. The results of analysis obtained by the proposed methods compared well with those obtained by corresponding pharmacopoeial methods. Recovery studies and statistical data proved the accuracy, reproducibility and the precision of the proposed methods. Presence of sodium benzoate did not interfere in analysis.

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“…The calibration curve of aceclofenac was prepared in distilled water and various concentrations of water soluble solubilizers (hydrotropic agents and cosolvents) at 274 nm using double-beam UV spectrophotometer (UV-1800, Shimadzu, Japan). [5][6][7]10] …”

“…Concentrated aqueous hydrotropic solutions of urea, nicotinamide, sodium benzoate, sodium salicylate, sodium acetate, and sodium citrate have been observed to enhance the aqueous solubility of many poorly water-soluble drugs. [3][4][5][6][7] Organic solvents and other cosolvents in parenteral formulations can lead to problems of toxicity, reduced blood compatibility, and injection difficulty because of increased vehicle viscosity. The vehicle should contain a minimum amount and low concentration of the co solvent.…”

“…Instead of using one solubilizer in large concentration for a desired level of solubility, the concentrated solutions made by employment of several solubilizers in small concentrations may show additive or synergistic enhancement in solubility. [10][11][12][13] Maheshwari proposed the concept of mixed solvency. He is of the opinion that all substances whether liquids, gases, or solids possess solubilizing power and hence concentrated aqueous solutions containing various dissolved substances can also improve the solubility of poorly water soluble drugs.…”

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“…The analysis of these poorly water soluble drugs and insoluble drugs were carried out by spectrophotometric estimation using organic solvents like methanol, chloroform, ethanol, benzene, acetone, toluene, carbon tetrachloride, diethyl ether and acetonitrile [2][3][4] . But the disadvantage of these organic solvents mentioned include costly, toxic and volatile in nature which would provide inaccuracy with the results 5 .…”

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“…S olid dispersion technique [1][2][3][4][5][6][7][8][9] has been utilized to increase the dissolution and thereby the rate of absorption and/or total bioavailability of poorly water-soluble drugs. The common methods of making solid dispersions are solvent evaporation, fusion, and fusion-solvent methods.…”