2.4. Design of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS)

SNEDDS were formulated with Labrafil^® M 1944 CS (constituting oil phase) and Kolliphor^® EL (non-ionic surfactant), and Transcutol^® P as a co-surfactant. Three terpenes (D-limonene, geraniol, and farnesol) were added, as 5% w/w of the oil phase, to determine their ASX skin permeation enhancement capability within the SNEDDS formulation. The physical characteristics and ASX skin delivery of all formulations were characterized, including the droplet size, polydispersity index (PDI), viscosity, ASX solubility, stability, oxidative inhibition values, and amount of ASX retained in the skin (IVPT).

The ratio of Labrafil^® M 1944 CS, Kolliphor^® EL, and Transcutol^® P was determined from ASX solubility experiments. The SNEDDS were prepared based on the method of Hong et al. [27], using a spontaneous emulsification method, and high energy input. Briefly, ASX (3 mg) was dissolved in 4 g of surfactant, stirred with magnetic stirring at 1000 rpm for 10 min. The mixture was then dissolved in 1 g of the oil phase, with magnetic stirring at 1000 rpm for 10 min. This mixture was then combined with 1 g of co-surfactant using magnetic stirring for 10 min, then sonicated in a water bath for 1 h at room temperature. The formulation vehicle addition sequence was based on preliminary ASX solubility determination in each vehicle component. A nanoemulsion formulation (L1-NE) was made by the same method but with an initial 6 mg ASX and then a 50:50 dilution with water as the final step to provide a nanoemulsion with the same ASX concentration as the SNEDDS formulations.

The composition of the SNEDDS formulations is documented in Table 1 with the initial SNEDDS formulation designated L1 and the terpene-containing formulation designated T1 (D-limonene), T2 (geraniol), and T3 (farnesol). All ASX SNEDDS were protected from light exposure at room temperature for further use.

ASX-SNEDDS formulation compositions (all excipients as w/w).

SNEDDS = self-nanoemulsifying drug delivery systems. L1 = initial formulation; T1 = addition D-limonene in oil phase; T2 = addition geraniol in oil phase; T3 = addition farnesol in oil phase. NE = nanoemulsion (50% water added to the oil/surfactant-cosurfactant mixture immediately before use). The final concentration of ASX in L1–NE was same concentration the SNEDDS.