Celecoxib Solubilization in Nonionic Microemulsions

Abstract

In this study, we report on the solubilization of celecoxib, a pharmaceutical active ingredient in the U-type microemulsions formulated using sucrose monolaurate and peppermint oil. Ethanol was used as the cosurfactant. The aqueous phase consisted of water + propylene glycol at a weight ratio equals two. The solubilization capacity of celecoxib in the formulated microemulsions along the water dilution line N60 where the surfactant/oil/ethanol weight ratio equals 3/1/1 is many times higher than in either the oil or the aqueous phase. The solubilized celecoxib does not affect the extent of water solubilization in the microemulsions. The celecoxib solubilization capacity decreases with the increase in the water content. We evaluated the microemulsions dilution and interfacial factors contributing to the celecoxib solubilization along the N60 dilution line. It was found that the dilution factor is dominant in determining the solubilization capacity of celecoxib when structural transitions are occurring. In an established microstructure, the interfacial factor is dominant. Structural transition of celecoxib loaded water-in-oil microemulsion to a bicontinuous phase and to oil-in-water droplets were identified using SAXS measurements along the N60 dilution line. It was found that below 30 wt% aqueous phase content the water-in-oil microemulsions are present, the transition between the water-in-oil to bicontinuous and then to oil-in water microemulsions occur at 30 and 75 wt% aqueous phase, respectively. SAXS measurements demonstrated that the drug effects the structure of microemulsion droplets and forms “ill-defined structures,” probably less spherical. Yet, the overall droplet sizes at the high dilutions did not change very much. The results demonstrate that the solubilized drug affects the transition from bicontinuous to water-in-oil microemulsions. The hydrodynamic radius of the drug loaded microemulsions at 80 and 90 wt% aqueous phase content was determined by dynamic light scattering.

Keywords:

• Correlation length
• dilution factor
• hydrodynamic radius
• interfacial contribution factor
• microstructure transitions
• periodicity
• solubilization capacity change factor