Hydroxypropyl Methylcellulose Acetate Succinate: Potential Drug-Excipient Incompatibility

被引：37

作者：

Dong, Zedong ^{[1
]}

Choi, Duk Soon ^{[1
]}

机构：

[1] Hoffmann La Roche Inc, Pharmaceut & Analyt Res & Dev, Nutley, NJ 07110 USA

来源：

AAPS PHARMSCITECH | 2008年 / 9卷 / 03期

关键词：

drug-excipient incompatibility; hot-melt extrusion; hydroxypropyl methylcellulose acetate succinate (HPMC-AS); solid dispersion; succinic acid;

D O I：

10.1208/s12249-008-9138-5

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The stability of hydroxypropyl methylcellulose acetate succinate (HPMC-AS) and its potential incompatibility with active pharmaceutical ingredients (API) carrying hydroxyl group(s) were investigated in this research. HPMC-AS may undergo hydrolysis under harsh processing conditions with the generation of succinic acid and acetic acid, which can form ester bond(s) with the hydroxyl group(s) in API. In this case, the hot-melt extrusion (HME) product prepared from HPMC-AS and our model compound (compound A) was tested after heating at 140 degrees C up to 5 h. The succinate esters of compound A and its epimer were found in the product, suggesting potential drug-excipient incompatibility during formulation development. In addition, dyphylline was also tested with HPMC-AS and the potential incompatibility was further confirmed.

引用

页码：991 / 997

页数：7

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