Dissolution Enhancement of Itraconazole by Hot-Melt Extrusion Alone and the Combination of Hot-Melt Extrusion and Rapid Freezing-Effect of Formulation and Processing Variables

被引：39
作者：
Lang, Bo [1 ]
McGinity, James W. [1 ]
Williams, Robert O., III [1 ]
机构：
[1] Univ Texas Austin, Coll Pharm, Div Pharmaceut, Austin, TX 78712 USA
来源：
MOLECULAR PHARMACEUTICS | 2014年 / 11卷 / 01期
关键词：
amorphous solid dispersion; hot-melt extrusion; formulation; process; screw design; dissolution; itraconazole; AMORPHOUS SOLID DISPERSIONS; ORAL ABSORPTION; PHASE-DIAGRAM; SUPERSATURATION; SOLUBILITY; DELIVERY; BIOAVAILABILITY; INDOMETHACIN; MISCIBILITY; POLYMERS;
D O I：
10.1021/mp4003706
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
We investigated the effects of the hot-melt extrusion (HME) process on the properties of itraconazole (ITZ) amorphous solid dispersions made by thin film freezing (TFF) technology. The ITZ-HPMCAS L (1:2) TFF composition exhibited limited drug release in acidic media. HME of the ITZ-HPMCAS TFF composition with hydrophilic carriers improved the drug release rate in acidic media. The type and level of hydrophilic carrier in the composition affected the dissolution profiles of the extrudates. A design of experiments (DoE) study was conducted to elucidate those effects. Hot-melt extrusion processing variables such as extrusion temperature and screw configuration also played a critical role on the properties of the extruded compositions. A higher degree of mixing reduced the crystallinity of semi-crystalline excipients and favored the drug release in the acidic media; moreover, the drug precipitation rate in the neutral pH media was reduced.
引用
收藏
页码：186 / 196
页数：11
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