Self-nanoemulsifying System Optimization for Higher Terconazole Solubilization and Non-Irritant Ocular Administration

Abstract

Purpose: Eye drops' formulations of poorly water-soluble drugs, offer the advantage of crossing the lipophilic cornea, but their limited aqueous solubility may lead to low ocular bioavailability limiting their therapeutic uses. Terconazole (TZ) is an antifungal drug with low aqueous solubility, restricting its application in ocular fungal infection. Thus, the aim of the work in this study is to enhance TZ solubilization, permitting better ocular permeation and higher bioavailability. To achieve this goal, different self-nanoemulsifying systems (SNESs) were prepared using different oils, surfactants and co-surfactants.

Methods: Ternary phase diagrams were constructed to identify self nano-emulsification regions for each oil system examined; either Labrafil (R) M2125CS or Capryol (TM) 90. TZ saturated solubility in the different formulated systems were measured and systems showing highest potential for TZ solubilization were selected. The optimized systems were chosen based on their globule size, polydispersity index, self-emulsification characteristics. Finally, TZ release as well as the irritation effect via Hen's Egg test-chorioallantoic membrane (HET-CAM test) of the optimized system was observed in vitro.

Results: The optimized system was formulated using 20% w/w Labrafil (R) M2125 CS, 50% w/w Tween (R) 80 and 30% w/w Transcutol (R) HP. Oil globules showed size range of 15.13 nm and self-emulsification time of 12.80 seconds. The system released 100% of the drug within half an hour compared to 2 hours in case of TZ-suspension. Finally, HET-CAM test showed non-irritating response and normal vascularization of the chorioallantoic membrane.

Conclusion: The formulated SNES could be a promising approach to enhance ocular efficacy of TZ