The importance of screening solid-state phases of a racemic modification of a chiral drug

Thermodynamic and structural characterization of solid-state phases of etiracetam

C. Herman, V. Vermylen, B. Norberg, J. Wouters, T. Leyssens

Research output: Contribution to journalArticle

Abstract

In this contribution different solid-state forms of the racemic compound (RS)-2-(2-oxo-pyrrolidin-1yl)-butyramide are studied from a structural and thermal point of view. Three different solid-state phases were identified, including two polymorphs and one hydrate phase. Comparison is made with the structure of the (S)-enantiomer, for which only one solid-state phase is known. The basic structural motif found in both polymorphs of the racemic compound is similar, but the basic motif observed for the hydrate differs. These synthons could in principle be used in future polymorph prediction studies to screen for possible alternative forms of the enantiopure compound. Based on the structure of the hydrate, further efforts should therefore be made in order to identify a hydrate structure of the enantiopure compound. Studying the different phases of a racemic compound can therefore help to guide polymorphic screening of an enantiopure compound.
Original languageEnglish
Pages (from-to)371-378
Number of pages8
JournalActa Crystallographica Section B: Structural Science, Crystal Engineering and Materials
Volume69
Issue number4
DOIs
Publication statusPublished - 1 Aug 2013

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etiracetam
Hydrates
hydrates
Screening
drugs
screening
Polymorphism
Thermodynamics
solid state
thermodynamics
Pharmaceutical Preparations
Enantiomers
enantiomers
predictions

Cite this

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abstract = "In this contribution different solid-state forms of the racemic compound (RS)-2-(2-oxo-pyrrolidin-1yl)-butyramide are studied from a structural and thermal point of view. Three different solid-state phases were identified, including two polymorphs and one hydrate phase. Comparison is made with the structure of the (S)-enantiomer, for which only one solid-state phase is known. The basic structural motif found in both polymorphs of the racemic compound is similar, but the basic motif observed for the hydrate differs. These synthons could in principle be used in future polymorph prediction studies to screen for possible alternative forms of the enantiopure compound. Based on the structure of the hydrate, further efforts should therefore be made in order to identify a hydrate structure of the enantiopure compound. Studying the different phases of a racemic compound can therefore help to guide polymorphic screening of an enantiopure compound.",
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AU - Norberg, B.

AU - Wouters, J.

AU - Leyssens, T.

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