LAUSR

Objective: The objective of the present work was to prepare and characterize grapefruit oil base microemulsions loaded with caffeine as a model hydrophilic compound. Methods: The formulation ingredients were selected based on surfactant efficiency and solubility studies. Ternary phase diagrams of grapefruit oil were constructed using the water titration method. Nine O/W microemulsions were constructed and prepared by mixing surfactant system, grapefruit oil, water and caffeine together. The resulting microemulsions were investigated for viscosity using Brookfield viscometer, for pH value using a digital pH meter, and for average particle size and polydispersity index (PDI) using a Zetasizer Nano. Ex vivo skin permeation through porcine ear skin was conducted using a side-by-side diffusion cell. The amount of caffeine was analyzed using HPLC-UV method. Results: Tween 20 yielded the highest emulsification ability for grapefruit oil and the highest caffeine solubility. It was selected as a major surfactant. Caffeine was slightly soluble in ethanol and isopropyl alcohol, but sparingly soluble in propylene glycol (PG). These ingredients were used as the cosurfactants. Nine grapefruit oil base microemulsions were prepared and characterized. The pH of microemulsions was within the range of 4.48-5.96. Particle size was in the range of 10.81±0.03 to 62.18±21.04 µm with the PDI of 0.13±0.02 to 0.64±0.11. Viscosity and particle size of microemulsions increased significantly with increasing grapefruit oil or tween 20 content. Addition of PG as cosurfactant resulted in the increases of viscosity, particle size and PDI. Depending on the formulation parameters, the permeation fluxes of caffeine from grapefruit oil base microemulsions were in the range of 28.4±3.4-361.4±15.2 µg/cm2/h. Conclusion: The grapefruit oil base microemulsions were successfully formulated. The physical properties and caffeine permeation of these microemulsions were found to be dependent on the grapefruit oil content, tween 20 content, cosurfactant type and content, as well as caffeine loading. The optimal formulation of grapefruit oil base microemulsion suggested composition of 5% grapefruit oil, 50% surfactant system (tween 20 and ethanol at the ratio of 9:1), and water.