A peculiar dehydration and solid–solid phase transition of the active pharmaceutical ingredient AZD9898 based on in situ single crystal-to-single crystal transformations,CrystEngComm

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A peculiar dehydration and solid–solid phase transition of the active pharmaceutical ingredient AZD9898 based on in situ single crystal-to-single crystal transformations
CrystEngComm ( IF 2.6 ) Pub Date : 2020/03/25 , DOI: 10.1039/d0ce00276c
Anna Pettersen _{1,

2,

3,

4,

5} , Okky Dwichandra Putra _{4,

5,

6,

7,

8} , Mark E. Light _{9,

10,

11,

12,

13} , Yukiko Namatame _{14,

15,

16}

Affiliation

Early Product Development and Manufacturing
Pharmaceutical Sciences
BioPharmaceuticals R&D
AstraZeneca Gothenburg
Mölndal SE-431 83
New Modality and Parenteral Development
Pharmaceutical Technology and Development
Sweden
UK National Crystallography Service
School of Chemistry
Faculty of Engineering and Physical Sciences
University of Southampton
SO17 1BJ Southampton
Rigaku Corporation
Tokyo 196-8666
Japan

AZD9898 has previously been used as a candidate for a potentially active pharmaceutical ingredient. AZD9898 form A hydrate was discovered during development and this form undergoes dehydration upon heating to give anhydrous form B. Further heating results in a solid–solid phase transition to a new anhydrous phase, form C. This study reports the crystal structures of form A, B, and C obtained by heating the single crystal of form A in situ on the diffractometer which establish the dehydration and solid–solid phase transition mechanisms. The dehydration from form A hydrate to form B anhydrous is an isostructural process while the solid–solid phase transition from form B to form C requires major structural changes. The relevant thermal profiles and vapour sorption behaviour of these forms are also reported in this study.

中文翻译：

基于原位单晶至单晶转化的活性药物成分AZD9898的特殊脱水和固-固相变

AZD9898以前曾被用作潜在活性药物成分的候选物。AZD9898的A型水合物在显影过程中被发现，加热时会脱水，生成无水B型。进一步加热会导致固-固相转变为C型新的无水相。这项研究报告了A型的晶体结构，通过原位加热形式A的单晶获得B和C在建立脱水和固-固相变机理的衍射仪上。从形式A的水合物脱水到形式B的脱水是一个同构过程，而从形式B到形式C的固-固相转变需要重大的结构变化。在这些研究中还报告了这些形式的相关热曲线和蒸气吸附行为。

更新日期：2020-04-03

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