目的 研究秦皮温敏眼用即型凝胶的体外性质，刺激性，药物释放机制及眼部消除动力学。方法 采用无膜溶蚀模型研究药物的释放机制。以凝胶外观、pH值、胶凝温度、含量等变化为指标考察强光照射、冷冻及加速实验条件下凝胶的稳定性。采用Draize眼部刺激性试验评价单次和多次给药后凝胶对兔眼的刺激性。使用统计矩法评价了药物在家兔眼部的消除动力学特征。结果 该制剂稳定性好，无刺激，药物释放主要受胶凝溶蚀控制，符合零级动力学过程。药动学结果显示，凝胶组AUC和MRT明显高于滴眼液组(P<0.05)。结论 秦皮温敏眼用即型凝胶可明显延长药物在眼部的滞留时间，提高药物的生物利用度，展现出良好的眼部应用前景。
Abstract
OBJECTIVE To study on characterization, irritation,the release mechanism and the elimination kinetics of Fraxini Cortex thermosensitive in-situ-forming eye gel (FC-ISG).METHODS The non-membrane dissolution model was used to observe the release mechanism of FC-ISG. The stabilities of FC-ISG were investigated under following circumstances bright light, freeze test and accelerating test.Single-dose and multiple-dose irritations of FC-ISG were evaluated by draize test.The elimination kinetics of FC-ISG were analyzed by non-compartment model.RESULTS FC-ISG showed good stability and non-stimulation to rabbit eyes.Drug release from FC-ISG was completely controlled by gel erosion, the release kinetics was coincided with zero-level release.AUC and MRT in FC-ISG group were significantly higher than those in control group (P<0.05). CONCLUSIONS FC-ISG can improve the bioavailability of drug by prolonging the residence retention time of drug in cornea. FC-ISG shows a great potential in ocular application.
关键词
秦皮 /
温敏 /
眼用即型凝胶 /
无膜溶蚀模型 /
生物利用度
{{custom_keyword}} /
Key words
Fraxini Cortex /
thermosensitive /
in-situ-forming eye gel /
non-membrane dissolution model /
bioavailability
{{custom_keyword}} /
中图分类号：
R944
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] LIU X,GAO S,YUAN Y F.Advances in drug-delivery systems of ophthalmic gel .China Pharm(中国药师),2009,12(11):1637.
[2] CHOI H G, JUNG J H, RYU J M, et al. Development of in situ-gelling and mucoadhesive acetaminophen liquid suppository. Int J Pharm, 1998, 165 (1): 33-44.
[3] ZHU Y Y, GAO Y S, XIAO J H, et al.Studies on the toxicity of indomethacin ophthalmic solution .J Taishan Med Coll (泰山医学院学报), 1995, 16(3):181-184.
[4] BHARDWAJ R, BLANCHARD J. Controlled release delivery system for the α-MSH analog Melanotan-I using poloxamer 407. J Pharm Sci, 1996, 85(9):915-919.
[5] DESAI S D, BLANCHARD J. In vitro evaluation of pluronic F127-based controlled release ocular delivery systems for pilocarpine. J Pharm Sci, 1998, 87(2):226-230.
[6] DING S L, CHEN C C, SALOME K R, et al. Precorneal sampling techniques for ophthalmic gels. J Ocular Pharmacol, 1992, 8(2):151-159.
[7] MA W D, XU H, NIE S F, et al. Temperature-responsive, pluronic-g-poly (acrylic acid)copolymers in situ gels for ophthalmic drug delivery: rheology, in vitro drug release, and in vivo resident property . Drug Dev Ind Pharm, 2008, 34(3):258-266.
[8] ZHANG J J, XIE K L, ZHAO N M, et al. Pharmacokinetics of topically applied in-situ-forming gels of fluconazole in rabbit eyes . Acta Pharm Sin(药学学报), 2000, 35(11):835-838.
[9] LI Y J, LIU X. Significance of determination the tears concentration of drugs in human eyes.Chin J Clin Pharmacol(中国临床药理学杂志), 2006, 26(5):397-398.
WILSON C G, ZHU Y P, FRIER M, et al. Ocular contact time of a carbomer gel (gel tears) in humans. Br J Ophthal Mol, 1998, 82(10):1131-1134.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
“十二五”国家科技重大专项重大新药创制资助项目(2014ZX09507001007);河北省卫生厅重点科技研究计划资助项目(20130455);河北省高等学校技术研究项目(QN20131011)
{{custom_fund}}
PDF(1419 KB)
