Comparison of different formulations of a novel rabbit derived Harderian nonpolar lipid on tear film stability in the dog

Abstract

Purpose : We have recently investigated the ability of a rabbit-derived tear film lipid, rabbit nonpolar lipid 593 (rNPL593), to prolong tear film stability in healthy dogs. Our data suggested that rNPL593 prolonged tear film breakup time (TFBUT) in healthy dogs. This study sought to compare two different formulations of rNPL593 and two different vehicles and determine its impact on TFBUT in dogs.

Methods : Six healthy Beagle dogs were treated in both eyes with a single dose of amorphous or crystalline rNPL593, suspended in vehicle with or without xanthum gum (XG) for a total of four different formulation/vehicle compositions. For each treatment, an ophthalmic examination using slit lamp biomicroscopy, the semi-quantitative preclinical ocular scoring (SPOTS) system, and TFBUT were performed at baseline (at least 24h prior to treatment), 6h- post treatment in the right eye and 24h- post treatment in the left eye. A minimum of 48h washout was established between treatments. Results for TFBUT were recorded in triplicate and presented as Mean Change from Baseline (MCB), and the different formulations were compared to their respective vehicle control.

Results : Treatments with all the topical formulations used were well-tolerated, with no signs of adverse effects when using the SPOTS system. Results of TFBUT demonstrated significant MCB at 6 hours after treatment with amorphous rNPL593, regardless of vehicle (without XG: 5.14 ± 1.02s, with XG: 3.59 ± 1.04s), when compared to solely vehicle control. However, at 24 hours post-treatment, TFBUT was no longer prolonged with the amorphous rNPL593 in XG. Conversely, the crystalline rNPL593 did not have a significant TFBUT MCB at 6 hours but was prolonged at 24 hours (without XG: 4.38 ± 1.44s; with XG: 3.98 ± 1.47s) when compared with their respective vehicle.

Conclusions : Crystalline and amorphous formulations for rNPL593 were effective in sustaining the positive effect on TFBUT; however, differences in particle morphology may affect formulation elution and stability, which can be related to the variance in TFBUT results over time. Further studies are necessary to elucidate long-term stability of the rNPL593 and if clinical results will be consistent in patients with DED.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Figure 1 – Different rNPL593 formulation processes prolong TFBUT in healthy dogs. XG: Xanthum Gum.