Abstract
Purpose :
The use of oil-in-water emulsions as vehicles for topical ocular delivery of lipophilic active ingredients aims at increasing the ocular permeability of those active ingredients by masking their lipophilic properties. To that end, the emulsion should stay composed, keeping the emulsion core-oil masked, while penetrating through those barriers. The purpose of this study is to get an insight on the in-vivo stability and longevity of the emulsion by comparing the pharmacokinetic faith of 14C-labeled core-oil, as a part of an assembled oil-in-water emulsion versus when it’s a solo component.
Methods :
A single 50 μl topical dose, of either a 14C-labeled core-oil of an assembled oil-in-water emulsion or a 14C-labeled core-oil-only, in the form of oil-in-water suspension, was administered to the cul-de-sac of one eye of an albino rabbit (2-2.5 kg). At 15, 30, 45, 60, 120, 180 and 360 min and 24 hrs. post dosing, 14C- determinations were carried out in harvested ocular tissues of the euthanized animals (n-4 at each time point). AUC of 14C determinations were calculated and Pearson correlation coefficients (PCC) were calculated for pairs of 14C- determinations along the eight time points.
Results :
For conjunctiva, the 14C determinations for core-oil were significantly higher than for the assembled emulsion at 45, 60 and 120 min (ratio 1.94, 1.74 and 2.08). AUC for 14C determinations was 64.54% higher for core-oil than for assembled emulsion. A strong positive correlation was found between the two sets of 14C determinations (PCC 0.762, p .028). The 14C determinations for assembled emulsion were significantly higher than for core-oil, for cornea (30, 45 and 60 min, ratio 1.79, 1.73 and 1.55) and posterior sclera (30, 45 and 60 min, ratio 2.48, 1.66 and 1.78). AUC for 14C determinations was significantly higher for assembled-emulsion compared to core-oil-only, without a significant correlation between the two sets of 14C determinations, for cornea (21.44%, PCC 0.488, p .220), for posterior sclera (44.47%, PCC 0.580, p .132) and for posterior retina (24.46%, PCC 0.407, p .317).
Conclusions :
The oil-in-water emulsion penetrated the ocular surface, significantly more than the core-oil through the cornea but through the conjunctiva as well, and reached the posterior segment, in part through the posterior sclera, and was largely assembled throughout the first hour post dosing.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.