The effect of pH, dilution, and temperature on the viscosity of ocular lubricants-shift in rheological parameters and potential clinical significance

Objective To investigate the effect of temperature, dilution, and pH on the viscosity of ocular lubricants. Design Laboratory based investigation of viscosity. Participants No human subjects. Methods Hypromellose 0.3%, sodium hyaluronate 0.4%, carboxymethylcellulose sodium 0.5%/glycerin 0.9%, and carmellose sodium 0.5% were investigated. Ostwald capillary viscometers were utilised for viscosity measurements. The kinematic viscosity of each lubricant was tested quantitatively from 22 to 40 degrees C, and over a pH range of 5-8 under isothermal conditions. The kinematic viscosity of each eye drop was also tested under dilution by varying the mass fraction of each eye drop under isothermal conditions. Main outcome measure Changes in kinematic viscosity. Results Hypromellose 0.3% had an initial pH of 8.34, while the other lubricants had a pH close to neutral. From 22 to 35 degrees C, the kinematic viscosity of sodium hyaluronate 0.4 fell by 36% from 37.8 to 24.4 mm(2)/s, carboxymethylcellulose sodium 0.5%/glycerin 0.9% fell by 35% from 16.98 to 11.1 mm(2)/s, hypromellose fell by 37% from 6.89 to 3.69 mm(2)/s, and carmellose sodium 0.5% fell by 25% from 2.77 to 1.87 mm(2)/s. At 32 degrees C only sodium hyaluronate 0.4%, and carboxymethylcellulose sodium 0.5%/glycerin 0.9% retained sufficient kinematic viscosity to maintain precorneal residence. Kinematic viscosities of all the topical lubricants were unaffected by pH but decreased significantly with dilution. Conclusions This study suggests that currently used ocular lubricants have limited bioavailability due to reductions in viscosity by temperature and dilutional changes under physiological conditions. Developing lubricants with stable viscosities may maximise therapeutic efficacy. Eye (2012) 26, 1579-1584; doi: 10.1038/eye.2012.211; published online 19 October 2012