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Ophthalmic formulation for delivery of lithium to the cornea

Other Titles
 리튬의 각막 전달을 위한 안약 제형/ 
Issue Date
2013
Description
Dept. of Pharmacy/석사
Abstract
The purpose of this study was to prepare an ophthalmic formulation of lithium using prodrug form of lithium fatty acid salt and surfactants to improve the permeation and accumulation. As lithium by itself was hard to pass through the dense lipophilic matrix of stratum cornea, we evaluated the barrier effect of cornea epithelium. Newzealand white rabbit was anesthetized by ether. The cornea was continuously scratched by #17 surgical blades. We administrated the eye drop containing lithium 10 times every 5 minute. Then, the rabbit was immediately sacrificed and the eye was enucleated within 15 minutes after the sacrifice. To analyze the lithium, all samples were quantified by atomic absorption spectrometry (AAS). Lithium concentration in scratched cornea was relatively increased from tenfold to thirtyfold. Since then, a dosing interval, a time of administration, dose, a concentration of lithium and analytical methods were the same. To find the formulation with enhanced permeability, we screened the various fatty acid and non-ionic surfactants. However, due to the drastic decrease in solubility and the rancid smell of lithium mono-carboxylic fatty acid salt, we choose the di-carboxylic acid. When the 0.17M lithium succinate (C4), Glutarate (C5), Adipate (C6) formulations were administered to rabbit eyes, lithium adipate (C6) formulation showed the about two times higher in lithium weight (0.805±0.035 μg) than others. The flux and permeability of 0.03M lithium Adipate (C6), Suberate (C8), Azelate (C9) formulations and formulations added non-ionic surfactant were measured by modified franz diffusion cell. The flux of lithium azelate (C9) formulation was 9.03 ± 0.95 (ng/cm2 per h) and the flux of lithium azelate (C9) formulation containing Cremophor® EL was 10.25 ± 0.76 (ng/cm2 per h). The flux of lithium suberate (C8) formulation containing TPGS was the same as lithium azelate (C9) formulation containing TPGS. Lithium azelate (C9) containing TPGS formulations of the pH 5 and 7 were administered to rabbit eyes. However, the lithium concentration of cornea did not show significant differences. Therefore, utilization of lithium azelate salts as the counter ion, and addition of Cremophor® EL and TPGS could be an effective way to make the ophthalmic drug solution with increasing the lithium penetration and accumulation in the cornea.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/134474
Appears in Collections:
2. 학위논문 > 5. Others > 기타 학위논문
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