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 þ 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.

Characterization of cephalexin loaded nonionic microemulsions

“…This slope change indicates the complete modification of the bicontinuous structure into oil-in-water droplets, and the water becomes the continuous phase. Similar behavior of the electrical conductivity of the drug free and drug loaded drug were reported elsewhere [19,20]. Fig.…”

“…2). Similar behaviors of solubilized drugs in microemulsions were reported elsewhere [19,20]. In order to further explain the changes in the solubilization of cephalexin in terms of microstructure changes we studied the electrical conductivity, ultra sonic velocity, density, particle size, and applied electron paramagnetic resonance spectroscopy.…”

“…Although solubilization of a variety of drugs has been reported in various types of microemulsions [4,9,19,20,24,34], cephalexin, a lipophilic antibiotic, is for the first time solubilized in pharmaceutically accepted microemulsions to be used for transdermal delivery.…”

“…At IF = 1, the interface and dilution factors contribute evenly, indicating that the drug is located partly at the interface and partly at the oil phase. When IF > 1, the interface plays a dominant role where the drug is mostly located at the interface [19,20]. As the IF grows, the interface plays a more significant role in the solubilization of the drug.…”

Solubilization of Azithromycin in Microemulsions Based on Mixed Nonionic Surfactants and Mixed Oils

“…This slope change indicatesthe complete change of the bicontinuousstructure into oil-in-water droplets, and the water becomes the continuous phase. Similar behavior of the electrical conductivity of the drug free and drug loaded drug were reported elsewhere [18,19]. …”