Development and optimization of drug-loaded nanoemulsion system by phase inversion temperature (PIT) method using Box-Behnken design.

Objective: The objective of the present investigation was to develop a stable and optimized drug-loaded nanoemulsion system using the phase inversion temperature (PIT) method.

Significance: The PIT method has been widely used for the development of food-grade nanoemulsion systems. For the first time, a simple and cost-effective, PIT method was used for the development of a stable drug-loaded nanoemulsion system.

Methods: Box-Behnken experimental design was used for the development of an optimized drug-loaded nanoemulsion system by the PIT method. The independent variables were optimized for responses by using the desirability function. The hydrophobic drug, benidipine was used as a modal drug. Optimized oil phase (blend of long-chain triglycerides oil, medium-chain triglycerides oil and essential oil) was used for the development of oil in water (O/W) nanoemulsion system.

Results: Optimum nanoemulsion formulation was stable, transparent and contained 50% of oil to surfactant percentage with a droplet size of 96.57 ± 1.61 nm. The optimum formulation also showed higher drug diffusion from dialysis membrane as compared to the marketed formulation. Nanoemulsion droplets were observed as spherical in the transmission electron microscopy (TEM) images. Box-Behnken statistical analysis revealed that all the independent variables had a significant impact on characteristics of nanoemulsion and the predicated value of independent variables was found to be valid.

Conclusion: It was concluded that the PIT method produces a stable and efficient drug-loaded nanoemulsion system. Further, the optimized oil phase can be used as an alternative to costly, commercial medium-chain triglycerides (MCT) oils, for the development of a stable nanoemulsion system.