Topical application currently serves as the main route for administering drugs for eye disorders. It is widely recognized that the efficiency of ophthalmic formulations are reliant on their rheology in such a way that when blinking submits the eyelid to a wide range of shear rates, the rheology of formulations must be carefully optimized. Knowledge about rheology and its impact on ophthalmology allows for residence time to be increased while maintaining maximal patient compliance.
Literature estimates that the shear rates during blinking are between 4000s-1 and 30 000s-1. Measuring viscosity through the use of conventional rheometers still pose a challenge for eye drops solutions that have low viscosity levels. The microfluidic system of FluidicamRHEO allows an accurate characterization of viscosity among representative shear values in just one single experiment.
Reminder of the Technique
Using a co-flow microfluidic principle to measure viscosity, FluidicamRHEO allows a sample and a reference solution to be introduced into the microfluidic channel (typically 2.2 mm X 150 μm) simultaneously and with controlled flow rates. This results in a laminar flow where the interface position between the sample and reference solution relates the viscosity ratio and flow rates.
Figure 1. Fluidicam measuring principle
Images taken during the measurement enable the software to calculate the interface position and directly plot an interactive flow curve.
Various commercialized eye drop formulations listed in the below table were analyzed using FluidicamRHEO at 34 °C (temperature of the corneal surface) over a large range of shear rates. Through the use of two microfluidic chips with 150 μm and 50 μm channel gap, respectively, shear rates ranging from 150s-1 to 100 000s-1 were applied.
M101440-CE_FORMULACTION_FLUIDICAM-V3 from Formulaction on Vimeo.
Viscosity as a Function of Shear Rates
Rheological properties change drastically depending on samples and the probed shear rate. With this, two sub-groups could be made:
Four samples, including Aqualarm, SyntaneUltra, Blink, and Systane balance, showed shear thinning behaviors with significant variations in viscosity.
The second group of samples, including Unilarm, Novoptine, and Ophtacalmfree, presented a Newtonian profile, with three overlapped flow curves around a viscosity value of ɳ=0.8 mPas.
These classes provide specific uses of the formulations, either topical eye treatment, drug delivery, or cleaning.
Figure 2. Viscosity profiles of several eye drops measured at 34 °C.
In order to acquire more insight on relative behavior, it is salient to fit the data with rheological models. The table below provides results of these calculations as determined by the Carreau Yasuda or Cross model.
Zero shear ɳ0 and infinite shear viscosity ɳ∞ may be computed using this method. The values presented provide a perspective on the liquid’s tendency to create discomfort, give rise to blurred vision, create resistance to blinking, and be washed out during tearing. The presented values also help in quantifying eye drop efficiency to maintain active substance in contact with the eye surface.
Table 1. zero and infinite shear viscosity values determined from the model fits.
The unique features of FluidicamRHEO enable operators to efficiently measure viscosity over a wide range of shear rates (ranging from 150 to 105s-1). This analysis is done in less than 3 minutes per sample and only requires 2.5 mL of sample volume. Using conventional rheology, the process would have taken 20 minutes and required 12 mL per sample, but still yield incomplete results. Application representative viscosity values facilitates the tuning of the desired eye drop formulation. It also helps to find the optimal setup required for various processes.
FluidicamRHEO facilitates an accurate method for measuring viscosity at a range of shear rates that are representative of the applied stress during blinking. The device provides relevant information that may be used in formulating eyedrop solutions for specific needs. Meanwhile, the use of microfluidic devices allows operators to perform precise characterization in just a couple of minutes using only a minimal sample amount.
This information has been sourced, reviewed and adapted from materials provided by Formulaction.
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