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阿托伐他汀钙三水合物是否具有熔点?

Does the trihydrate of atorvastatin calcium possess a melting point?

机构信息

SMS Laboratory (EA 3233), Université de Rouen-Normandie, Place Émile Blondel, Mont Saint Aignan 76821, France; Laboratory of Materials, Treatment and Analysis (LMTA), National Institute of Research and Physical-chemical Analysis, Technopark of Sidi-Thabet, Ariana 2020, Tunisia; Faculté des Sciences de Bizerte, Université de Carthage, Zarzouna Bizerte 7021, Tunisia.

Laboratory of Materials, Treatment and Analysis (LMTA), National Institute of Research and Physical-chemical Analysis, Technopark of Sidi-Thabet, Ariana 2020, Tunisia.

出版信息

Eur J Pharm Sci. 2020 May 30;148:105334. doi: 10.1016/j.ejps.2020.105334. Epub 2020 Apr 4.

Abstract

To decide whether an active pharmaceutical ingredient can be used in its amorphous form in drug formulations, often the glass transition is studied in relation to the melting point of the pharmaceutical. If the glass transition temperature is high enough and found relatively close to the melting point, the pharmaceutical is considered to be a good glass former. However, it is obviously important that the observed melting point and glass transition involve exactly the same system, otherwise the two temperatures cannot be compared. Although this may seem trivial, in the case of hydrates, where water may leave the system on heating, the composition of the system may not be evident. Atorvastatin calcium is a case in point, where confusing terminology, absence of a proper anhydrate form, and loss of water on heating lead to several doubtful conclusions in the literature. However, considering that no anhydrate crystal has ever been observed and that the glass transition of the anhydrous system is found at 144 °C, it can be concluded that if the system is kept isolated from water, the chances that atorvastatin calcium crystallises at room temperature is negligible. The paper discusses the various thermal effects of atorvastatin calcium on heating and proposes a tentative binary phase diagram with water.

摘要

为了确定药物制剂中是否可以使用某种原料药的无定形形式,通常会研究原料药的玻璃化转变温度与熔点的关系。如果玻璃化转变温度足够高,且发现其与熔点相对接近,则该原料药被认为是良好的成玻璃剂。然而,非常重要的是,观察到的熔点和玻璃化转变必须涉及完全相同的体系,否则无法对这两个温度进行比较。尽管这似乎微不足道,但在水合物的情况下,加热时水可能会离开体系,因此体系的组成可能不明显。阿托伐他汀钙就是一个很好的例子,其中混淆的术语、缺乏适当的无水形式以及加热时失水导致文献中出现了几个有疑问的结论。然而,考虑到从未观察到无水晶体,并且无水体系的玻璃化转变温度为 144°C,可以得出结论,如果将体系与水隔离开来,那么阿托伐他汀钙在室温下结晶的可能性可以忽略不计。本文讨论了阿托伐他汀钙在加热过程中的各种热效应,并提出了一个带有水的暂定二元相图。

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