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Peter A Simmons, Pasquale Aragona, Hongpeng Wang, Tao Wang; Polymer size and other physical properties vary among hyaluronic acid-based lubricant eye drops. Invest. Ophthalmol. Vis. Sci. 2017;58(8):454.
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© ARVO (1962-2015); The Authors (2016-present)
Hyaluronic acid (HA) solutions are often used for dry eye. HA polymer size may have a large range, with higher molecular weight (MW) considered more desirable for its ability to build viscosity at lower concentration, with decreased likelihood of inflammatory reactions. Some formulations combine HA with other polymeric ingredients, which may affect the observed molecular weight, other physical properties, and clinical performance. This study assessed the MW of the HA in commercial HA formulations, along with rheological performance as a predictor of clinical efficacy, and the total osmolality and sodium content.
MW and polydispersion index (PDI) of 18 commercial eye drops were measured using a light-scattering method on a Agilent Technologies 1200 series HPLC with a Dawn Heleos-II MALS detector and an Optilab rex RI detector (both from Wyatt Technology). Rheological performance was measured on an DHR-3 rheometer (TA Instruments), with shear rate varied from 1 to 10,000 reciprocal seconds. To further characterize formulations containing polymers in addition to HA, molecular weight analysis was repeated after hyaluronidase digestion. Total osmolality was determined with a standard osmometer, and sodium concentration ([Na+]) was determined by ICP-MS (Agilent).
MW ranged from 204 to 2026 kDa, with PDI from 1.05 to 4.94. Following hyaluronidase treatment, some products decreased and others increased overall MW, indicating that HA was the larger or smaller (respectively) polymer in a mixed-polymer formulation. 5 of the 18 formulations contained relatively low (<500 kDa) MW HA, and 4 had very high (>1000 kDa) MW HA. All formulations exhibited shear-thinning, with viscosity being a function of both MW and concentration. 3 formulations had low-shear viscosity above 40 cPs, and 7 had low-shear viscosity below 10 cPs. Total osmolality ranged from 154 to 335 mOsm/kg, and Na+ content from 22 to 183 mM. Osmolality was not strictlylinked to [Na+] due to contribution of alternative osmolytes.
Higher MW of HA allows higher low-shear viscosity at lower concentration; addition of another synergistic polymer may augment performance. Lower [Na+] may be desirable, as excess salt in the tear film is associated with up-regulation of inflammatory processes and ocular surface damage. Formulations with high-MW HA and alternative compatible osmolytes may be preferred for dry eye patients.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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