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. 2017 Sep 12:11:1637-1642.
doi: 10.2147/OPTH.S135550. eCollection 2017.

Investigating the potential benefits of a new artificial tear formulation combining two polymers

Peter A Simmons  1 , Joseph G Vehige  1
Affiliations

Investigating the potential benefits of a new artificial tear formulation combining two polymers

Peter A Simmons et al. Clin Ophthalmol. .

Abstract

Purpose: Artificial tear formulations typically contain a water-soluble polymer to enhance residence time, moisture retention, and binding to the mucin coat of the ocular surface, which facilitate corneal healing. This study investigated the potential advantages of combining carboxymethylcellulose (CMC) and hyaluronic acid (HA) polymers in a single formulation.

Materials and methods: Individual CMC and HA solutions were prepared and tested for bulk viscosity in comparison to a solution that combined CMC and HA. Rheometry determined the differences between solutions at increasing shear rates, simulating eye movement and blinking.

Results: The bulk viscosity of the individual 0.5% CMC and 0.1% HA solutions was 2.5 and 5.7 cP, respectively. The viscosity of the combined solution (13.1 cP) was 60% higher than predicted by additive effects. Rheometry revealed shear rates between 10/second (open eye) and 10,000/second (blinking eye). At these rates, viscosity ranged from 2.7 to 3.5 cP for 0.5% CMC, 2.8 to 6.8 cP for 0.1% HA, and 5.2 to 15.3 cP for the 0.5% CMC-0.1% HA combination. Low-shear viscosity of the CMC-HA combination increased 48% over the sum of the individual solutions, but high-shear viscosity remained virtually unchanged. Data from CMC and HA solutions at higher concentrations were consistent with these results.

Conclusion: Combining CMC and HA polymers produced a synergistic increase in low-shear viscosity (which cannot be fully explained by simple molecular entanglement), while the high-shear viscoelasticity of the combined solution remained unaffected. These data suggest that CMC-HA combinations have properties that may be used to formulate artificial tears that optimize ocular retention (through higher low-shear viscosity), while minimizing blur and stickiness during blinking (through lower high-shear viscosity).

Keywords: artificial tear; carboxymethylcellulose; dry eye; eyedrop; hyaluronic acid.

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Conflict of interest statement

Disclosure PAS and JGV are employees of Allergan plc and report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Structure of CMC and HA. Notes: (A) In solution, CMC forms a relatively short linear polymer (n~400); (B) compared with CMC, HA is a much longer polymer (n>5,000) that forms a random, globular coil in solution, rather than being linear. Abbreviations: CMC, carboxymethylcellulose; HA, hyaluronic acid.
Figure 2
Figure 2
Rheological analysis of combinations of low (A), medium (B), and high (C) concentrations of CMC and HA polymers. Notes: Data points represent mean ± standard deviation. Viscosity and shear rate are presented on a log scale. Abbreviations: CMC, carboxymethylcellulose; HA, hyaluronic acid.
Figure 3
Figure 3
Bulk viscosity of the combined solution of 0.5% CMC and 0.1% HA was higher than predicted by additive effects. Note: Data represent mean ± standard deviation Brookfield viscosity at 60 rpm (approximately equivalent to 79.2/second). Abbreviations: CMC, carboxymethylcellulose; HA, hyaluronic acid.
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