alexa Abstract | A comparative solubility enhancement profile of valdecoxib with different solubilization approaches

Indian Journal of Pharmaceutical Sciences
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Research Paper Open Access

Abstract

Solubility enhancement of poorly aqueous soluble drug is an important aspect of formulation development. Although there is plethora of reports of solubility improvement using different techniques, a comparative study of different solubilization approaches are few. Valdecoxib chemically designated as 4-(5-methyl-3-phenyl-4-isoxazolyl) benzenesulfonamide is a novel potent COX-2 inhibitor having poor aqueous solubility (10 mg/ml). Since it is poorly water-soluble, various techniques could be applied to increase its aqueous solubility. Objective of present study was to provide a comparison of effect of various solubilization techniques, namely micellar solubilization, cyclodextrin complexation and cosolvency, on solubility of valdecoxib. Solubility of valdecoxib was determined in various ionic and nonionic surfactants using phase solubility analysis. Similar type of study was performed using different water:cosolvent mixture. In addition, solubility improvement by use of 2 novel hydrophilic β -cyclodextrin derivatives, hydroxypropyl β -cyclodextrin and sulfobutyl ether-7-β -cyclodextrin was examined. Results showed that highest solubility (70 fold) was achieved with use of Cremophor EL followed by Tween 80 and sulfobutyl ether-7-β -cyclodextrin. It was found that surfactants with higher HLB values were better solubilizers. Solubilization capacity was found to increase with increase in hydrocarbon chain of surfactant, suggesting hydrocarbon core of micelles as locus of solubilization. Similarly, less polar solvents were found to increase solubility by greater extent, thus accentuating hydrophobic interaction mechanism. Among cyclodextrin, higher binding constant and solubility enhancement was obtained by use of sulfobutyl ether-7-β -cyclodextrin. Thus, the study generated an important dataset so as to compare effect of various solubilizers on solubility of valdecoxib.

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Author(s): A Modi P Tayade

 
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