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Christoph Luschmann, Olaf Strauss, Joerg Tessmar, Karl Luschmann, Achim Goepferich; In-situ Nanosuspensions - A Novel Approach Towards The Ocular Administration Of Poorly Water-soluble Drugs. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3758.
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Ophthalmic diseases like keratokonjunctivitis sicca are usually treated with lubricants, even though drugs like Cyclosporine A (CsA) are known to be efficient tools for a causal therapy. Unfortunately, CsA suffers like a number of other drugs from low solubility in water and can, therefore, not be administered via aqueous eye drops. Oily eye drops on the other hand lead to irritations on the eye surface. We hypothesize that liquid Polyethylene Glycoles (PEGs) would be potent solvents for CsA. Moreover upon contact with the tear fluid a spontaneous in-situ nanoprecipitation of drug could be induced.
CsA was kindly donated by Pharma Stulln GmbH, Polyethylene Glycol Dimethylether (MW= 500Da) by Clariant Produkte GmbH and Solutol® HS15 by BASF.For turbidimetric analysis absorption was measured in 96-well-titerplates using a Shimadzu UV/VIS-platereader at = 550nm. Particle sizes were determined using dynamic light scattering (PCS) with a Malvern® Zetasizer Nano. Light microscopic pictures were taken using a Zeiss® confocal microscope in combination with the ZEN Software of Zeiss.
The turbidimetric data showed that with decreasing levels of drug the amounts of water, necessary to induce a precipitation, increased. The presence of Solutol® could increase these levels further up to 70% water for 0.5% CsA. Preparations with Solutol® showed much more homogenous and stable dispersions with particle sizes below 10µm under the light microscope. The PCS confirmed this result. The particle sizes were around 200nm and depended on the Solutol®/CsA ratio. The different sizes obtained by PCS and microscopy seem to be results of the different samples preparation methods.
The results show, that an "in-situ nanosuspension" might be an efficient way to administer poorly water soluble drugs to the eye. The optimization of this approach seems to be a promising way to novel formulations for the causal treatment of keratokonjunctivitis sicca.
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