Consideration on the formulation of benzoyl peroxide at ambient temperature: choice of non-polar solvent and preparation of submicron emulsion gels

The aim of this study performed at ambient temperature was first to determine the solubility of benzoyl peroxide in various solvents with a large range of polarity. All these solvents can be used in the dermatological field. Then, using the most suitable solvent, a new drug vehicle submicron oil-in-water emulsion was formulated. Correlation between dielectric constant (ε) and drug solubility in various solvents and different binary mixtures was verified. An original ternary diagram with surfactant-co-surfactant/oil/water was performed at low temperature to determine the regions of submicron emulsions. A dramatic change in the magnitude of benzoyl peroxide solubility occurred above a dielectric constant value of about 20. The solubility of this drug can be enhanced by the replacement of polar solvent by a vehicle of lower dielectric constant. A stable submicron emulsion gel was made with cremophor EL, glycerol, caprilic-capric triglycerides, and water in the proportion of 20-20/35/25, respectively; 1.5% benzoyl peroxide was also added. This submicron emulsion vehicle consisted of oil droplets, with a mean diameter of approximately 100-150 nm, dispersed in a continuous water phase. These studies confirm the potential of benzoyl peroxide incorporation into submicron emulsion gel and the stability of this formulation.