Investigation of the polymorphism of the angiotensin II antagonist agent MK-996

被引：9

作者：

Jahansouz, H ^{[1
]}

Thompson, KC ^{[1
]}

Brenner, GS ^{[1
]}

Kaufman, MJ ^{[1
]}

机构：

[1] Merck Sharp & Dohme Ltd, Merck Res Labs, Dept Pharmaceut Res, W Point, PA 19486 USA

来源：

PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY | 1999年 / 4卷 / 02期

关键词：

angiotensin II antagonist agents; heat of solution; polymorphism; solubility; stability;

D O I：

10.1081/PDT-100101352

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The polymorphism of the angiotensin II antagonist agent MK-996 was studied, with particular emphasis on crystal form stability, solubility, and reproducible crystallization of the drug. X-ray powder diffraction patterns indicated differences in the crystal forms of early research and development lots. Solubility data for the different crystal forms in water at 25 degrees C are in agreement with the solution calorimetry data and indicated that crystalline form I is the thermodynamically stable polymorph of MK-996 under ambient conditions. In contrast to the other polymorphs, form I is reproducibly prepared an both the laboratory and production scale. This study examines methodology to determine the most suitable polymorph for development.

引用

页码：181 / 187

页数：7

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