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Howard A. Ketelson, James W. Davis, Minrui Chen, Yuguo Cui, Robert Pelton; Towards Photochemical Measurement of Nano-Emulsion Lubricant Eye Drop Coalescence in the Tear Film. Invest. Ophthalmol. Vis. Sci. 2012;53(14):304.
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A challenge in the formulation of emulsion eye drops containing polymer, lipids and oil ingredients is to maintain colloidal stability without impacting performance in the eye. Ideally, emulsion droplets are indefinitely stable towards creaming and coalescence until they are dropped onto the eye whereupon there is breakdown, release and retention of the critical chemical components in the eye. We have developed photochemical approaches to tracking nano-emulsion colloidal stability. The method has been demonstrated in vitro with the potential to perform real-time emulsion stability measurements in the tear film.
Two samples of negatively charged oil-in-water nano-emulsions stabilized with phosphatidylcholine (PC) were prepared. The average diameters were controlled by the processing conditions and could be varied between 100 and 250 nm. One emulsion sample was doped with nitrobenzyldiazol-labeled PC, the donor, and the other with rhodamine B- labeled PC, the acceptor. The two types of labeled emulsions were mixed and emulsion aggregation was measured by Fluorescence Resonance Energy Transfer (FRET),that reports a change in the fluorescent spectrum when the donor and acceptor come in contact. The FRET-based approach for monitoring nano-emulsion stability was validated by traditional dynamic light scattering methods.
Hexadecane nano-emulsions were mixed with three guar derivatives to induce either: 1) no effect in the presence of low molecular weight partially hydrolyzed guar; 2) depletion flocculation and coalescence, induced by high molecular hydroxypropyl guar; or, 3) bridging flocculation (cationic guar). FRET was a sensitive probe for depletion induced coalescence but was not a sensitive measure of bridging flocculation where the emulsion droplets have little opportunity to coalesce.
We have demonstrated that FRET is a sensitive measure of nano-emulsion stability and that it may be useful for tracking emulsion distribution and delivery mechanisms in the tear film.
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