Salt selection and simultaneous polymorphism assessment via high-throughput crystallization:: The case of sertraline

被引：66

作者：

Remenar, JF ^{[1
]}

MacPhee, JM ^{[1
]}

Larson, BK ^{[1
]}

Tyagi, VA ^{[1
]}

Ho, JH ^{[1
]}

McIlroy, DA ^{[1
]}

Hickey, MB ^{[1
]}

Shaw, PB ^{[1
]}

Almarsson, Ö ^{[1
]}

机构：

[1] Transform Pharmaceut Inc, Lexington, MA 02421 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2003年 / 7卷 / 06期

关键词：

D O I：

10.1021/op034115+

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

High-throughput (HT) crystallization experiments were conducted with sertraline free base in the presence of mono-, di- and triacidic salt formers. Over 3600 crystallization trials were conducted, leading to the identification and characterization of 18 crystalline salt forms. Due to the large number of crystallization conditions for a given salt type, it was possible to gauge the propensity of a given salt form to exhibit polymorphism. Four salt forms were found to exist (in this limited screen) as monomorphic materials. Unlike the HCl salt in the marketed drug product, the HBr salt appears resistant to polymorphism, crystallizing as a single form from over 140 discrete trials. This observation underscores the lack of predictability of polymorphic behavior of pharmaceuticals even when seemingly minor changes to the composition are made. The experiments highlight the importance of coupling salt selection studies with simultaneous polymorph screening to gain a more comprehensive understanding of solid form diversity as part of the form selection process for pharmaceutical development.

引用

页码：990 / 996

页数：7

共 21 条

[1]

ALMARSSON O, 2003, IN PRESS CRYST GROWT

[2] Ritonavir: An extraordinary example of conformational polymorphism [J].