Introduction
Ophthalmic Viscosurgical Devices (OVDs) are viscoelastic solutions or gels used to protect the corneal endothelium from mechanical trauma and to maintain intraocular space during eye surgery. They usually contain one or more of the following components; hyaluronic acid or its sodium salt, chondroitin sulfate or methylcellulose. As these materials are polymeric, they tend to be viscoelastic with their properties strongly dependent on factors such as concentration, molecular weight and molecular architecture as well as intra- or inter- molecular interactions in solution.OVDs can be classified according to their ‘cohesiveness or dispersiveness’ which are ultimately related to their rheological properties. Cohesive OVDs are high viscosity materials that adhere to one another through molecular associations. They tend to have higher molecular weights and are highly shear thinning with high surface tension. Because of their high viscosity, cohesive OVDs are able to pressurize the eye and create space for insertion of the optical implant (lens). Their cohesiveness also facilitates easy removal at the end of surgery as the entire mass sticks together. In contrast, dispersive OVDs tend to be lower in molecular weight and are more Newtonian. They have lower viscosities and lower surface tension making them better able to coat and adhere to both tissues and surgical instruments, and also help lubricate the optical implant during insertion. Dispersive OVDs tend to be more difficult to remove after surgery due to their higher fluidity. In addition to the two classes just described, there are also combination OVDs which incorporate dispersive and cohesive properties, and visco-adpative OVDs that display different properties depending on the conditions of use. There is now an International Standard (ISO15798:2013) detailing the requirements for characterizing these materials in terms of their biological, chemical and physical characteristics. For the purpose of this application note, we are concerned with the section of the standard relating to rheological characterisation. The standard states that the product should be tested in its finished and sterilized state at 25ºC for rheological testing and involves both oscillatory and steady shear testing respectively for characterising both viscoelastic and flow characteristics in terms of the dynamic viscosity, complex viscosity and viscoelastic moduli. The complex viscosity is measured as function oscillation frequency using logarithmic increments to simultaneously demonstrate the resistance to flow and deformation of the OVD formulation. The frequency range specified is between 0.001 Hz and 1000 Hz but 0.01 to 100Hz is considered acceptable so long as the zero shear viscosity plateau (at diminishing frequencies) is accessible. This will occur at lower frequencies for higher viscosity materials. Often it is not possible to achieve 100Hz on a rotational rheometer due to inertial limitations and hence one should aim for the highest achievable frequency. The elasticity or viscoelasticity of the OVD is characterised through G’ and G” and is measured simultaneously with η* up to a frequency of 100Hz ideally, or as high as is possible considering inertia limitations. Data should either be presented on a double logarithmic scale against frequency or as a plot of percent elasticity against log frequency, for example as 100 × [G′/ (G′+G′′)] versus log frequency. For steady shear measurements, the suggested shear rate range is from 0.001s-1 to approximate the zero shear viscosity, representative of conditions within the anterior chamber, to a shear rate of approximately 100s-1, to replicate conditions when the viscoelastic fluid is being injected into the eye through a cannula. The shear rates should be increased in logarithmic increments and steady shear viscosity data presented as a function of shear rate on a double logarithmic scale. As measuring low viscosity fluids at low shear rates can be problematic, the lowest shear rate at which the zero shear viscosity can be attained is deemed acceptable. The zero shear viscosity plateau tends to appear at higher shear rates for low viscosity materials and lower shear rates for high viscosity materials, so low shear rates are not always needed. Note that the steady shear zero shear viscosity should correspond with the equivalent value of η* measured using oscillatory testing.
Experimental
- An OVD formulation containing hyaluronic acid at three different concentrations 15mg/ml, 18mg/ml and 25mg/ml was analyzed and compared according to ISO15798:2013
- Rotational rheometer measurements were made using a Kinexus rotational rheometer with a Peltier plate cartridge and using 4°/40mm cone-plate measuring system for oscillatory measurements and a 2°/20mm cone-plate for viscometry tests
- A standard loading sequence was used to ensure that both samples were subject to a consistent and controllable loading protocol. All rheology measurements were performed at 25°C.
- A strain controlled frequency sweep within the pre-determined linear viscoelastic was performed to determine G’,G” and η* as a function of frequency
- An equilibrium table of shear rates test was performed to determine the steady state shear (dynamic) viscosity as a function of shear rate
- Values of η0 were attained by means of a Cross-model analysis within the rSpace software.
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