摘要
目的 采用流化床包衣工艺制备速释型伊曲康唑固体分散体载药微丸。方法 以常见的亲水性辅料为载体材料,溶剂法制备水不溶性药伊曲康唑的固体分散溶液,然后将其喷雾干燥共沉淀于流化床底喷锅内的蔗糖丸芯表面上,直接形成速释型伊曲康唑固体分散体载药微丸,并对其药物溶出度、晶型表征、外观性状、以及溶剂残留等进行系统评价。结果 制备的伊曲康唑载药微丸外观光洁美观,药物以无定形或分子态存在于载药层中,符合固体分散体结构特征。HPMC E5/伊曲康唑(1.5∶1,w/w)固体分散体载药微丸的药物溶出迅速,15 min可达80%以上。为保证溶剂残留在药典规定的限度内,制备的伊曲康唑载药微丸需要在真空80 ℃干燥6 h以上。结论 采用流化床底喷上药包衣技术制备速释型伊曲康唑固体分散体载药微丸,质量可控,工艺可行。
Abstract
OBJECTIVE To develop immediate-released itraconazole-loaded pellets prepared by fluidized bed spray coating. METHODS With common hydrophilic excipients(HPMC E5, PVP K30, PEG6000, and Poloxamer 188)as the carrier material, solid dispersion solution(dichloromethane-ethanol, 1∶1, V/V)containing water-insoluble itraconazole was prepared, and then was sprayed on the surface of the sugar cores in fluidized bed to directly form immediate-reaease drug-loaded pellets containing itraconazole solid dispersion. Subsequently, its drug dissolution, crystal characterization, appearance, and residual solvent were evaluated. RESULTS The obtained pellets are clean and beautiful appearance. And itraconazole in the drug-loaded layer exists in amorphous or molecular state, meets with the solid dispersion structure. It was interesting that, the pellets containing HPMC E5/itraconazole(1.5∶1, w/w)solid dispersion were of rapid drug dissolution(15 min up to 80%). To ensure that residual solvent within the limits, it was necessary that the obtained pellets were dried more than 6 h at 80 ℃ in vacuum. CONCLUSION It is feasible that immediate-release itraconazole-loaded pellets are prepared by fluidized bed spray coating technology, and its quality could be controlled.
关键词
流化床包衣技术 /
伊曲康唑 /
固体分散体 /
羟丙甲纤维素 /
微丸 /
溶出度
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Key words
fluidized bed spray coating /
itraconazole /
solid dispersion /
HPMC E5 /
pellet /
dissolution
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单利,史焱,王玉丽,赵琳琳,杨美燕,蒋庆宇,高春生.
基于流化床包衣工艺的伊曲康唑速释微丸的制备和评价研究[J]. 中国药学杂志, 2013, 48(1): 54-58
SHAN Li, SHI Yan, WANG Yu-li, ZHAO Lin-lin, YANG Mei-yan, JIANG Qing-yu, GAO Chun-sheng.
Formulation and Characterization of Immediate-Release Itraconazole-Loaded Pellets Prepared by Fluidized Bed Spray Coating[J]. Chinese Pharmaceutical Journal, 2013, 48(1): 54-58
中图分类号:
R944
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参考文献
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JANSSENS S, ARMAS H N D, ROBERTS C J. Characterization of ternary solid dispersions of itraconazole, PEG 6000 and HPMC 2910 E5 . J Pharm Sci, 2008, 97(6): 2110-2120.
JUNG J Y, YOO S D, LEE S H, et al. Enhanced solubility and dissolution rate of itraconazole by a solid dispersion technique . Int J Pharm, 1999, 187(2): 209-218.
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脚注
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基金
国家科技重大专项—综合性新药研究开发技术大平台资助项目(2012ZX09301003-001-009)
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