Unveiling the dielectric properties of self-nanoemulsifying drug delivery systems (SNEDDS)

Self-nanoemulsifying Drug Delivery System (SNEDDS) improves the bioavailability of bioactive compounds that exhibit low water solubility. In this regard, our study aims to assess the formulation of SNEDDS in a wide range of oil concentrations (0-8.6 wt%) by dynamic light scattering, FTIR, dielectric measurements, and the characterization of the interface layer and its molecular interactions with water. The proper formulation of SNEDDS accounted for the lipophilic/hydrophilic balance leading to a homogeneous distribution of oil droplets in water with constant sizes of 20-22 nm, which does not depend on oil concentration. Dielectric spectroscopy measurements in the GHz frequency range allowed us to obtain the dependence of relaxation time as a function of oil concentration and its relationship with the viscosity of the nanoemulsion. The classical two-phase model of Hanai, Maxwell-Garnet, Bruggeman, and Lichtenecker fails to describe the dielectric properties of nanoemulsions. Therefore, in this work, a three-phase model is proposed to model the dielectric measurements, which include water as the continuous phase, oil droplets, and interface layer due to using Cremophor EL (HLB = 12-14) and Labrafil M1944CS (HLB = 2-3) as surfactant and co-surfactant. This model fits well with the experimental results and allows us to obtain SNEDDS properties such as the dielectric constant (20.9), volume fraction, and the interface layer thickness (ca. 5 nm). Investigated oil-water nanoemulsions can be a model for developing different drug delivery systems. Additionally, proposed measurements in the GHz frequency range and their interpretation can be generalized for nanoemulsion characterization. (c) 2023 Elsevier B.V. All rights reserved.