SOLUBILIZATION OF CELECOXIB USING ORGANIC COSOLVENT AND NONIONIC SURFACTANTS OPTIMIZED BY EXPERIMENTAL DESIGN
Abstract
Objective: The solubility of drug substances in water is one of the major factors taken into account in the formulation of oral solutions and parenteral forms. The present study aims to evaluate the utility of a mixture design in improving water solubility of celecoxib through a micellar system by the use of organic co solvent and nonionic surfactants that are well tolerated by the parenteral route.
Methods: In our study, a design of experiments approach was tested using a mixture design of nonionic surfactants (Tween® 80 and Solutol®HS 15), an organic cosolvent (ethanol) and celecoxib. Solubility determination was based on the analysis of samples absorbance at 215 nm. A particles size measurement was conducted using a Dynamic Light Scattering at the point showing the maximum of solubility.
Results: The results showed a significant solubility increase in most of tested mixtures. The analysis of the design space showed that the solubility of celecoxib varies very closely with the concentration of Tween® 80 associated with ethanol and Solutol®HS 15 in water. Run 19 containing 0.8% of celecoxib, 10% of ethanol, 2% of Tween® 80, 2% of Solutol®HS 15 and water q. s. for 100% w/w improved celecoxib solubility by about 90 %, and showed an average particles size of 9.67 nm.
Conclusion: Micellar solubilisation associating a cosolvent and nonionic surfactants seems to improve celecoxib solubility significantly. Mixture design provides maximum information about the effects and the proportions of each component from a limited number of experiments.
Keywords: Solubility, Celecoxib, Mixture design, Cosolvent, SurfactantsÂ
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References
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