Polymorph Stability Prediction: On the Importance of Accurate Structures: A Case Study of Pyrazinamide

Wahlberg, Nanna; Ciochoń, Piotr; Petřı́ček, V.; Madsen, Anders Ø.

doi:10.1021/cg400800u

Cited by 20 publications

(29 citation statements)

References 23 publications

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“…A number of modelling studies involving PZA have been published. The most extensive is that of Wahlberg et al demonstrating and quantifying disorder in the structure of the g form (Wahlberg et al, 2013) as mentioned before by Cherukuvada et al (Cherukuvada et al, 2010). Computational studies specifically targeting the b form of pyrazinamide have been published by Jarzembska et al (Jarzembska et al, 2014).…”

Section: P1 "mentioning

confidence: 99%

“…In the g form, the molecules are arranged in catemers with hydrogen bonds linking the amide group with the top of the pyrazine ring. The g polymorph exhibits disorder in which for about 20 % of the molecules the position of the ring and the amide group are inversed (Cherukuvada et al, 2010;Wahlberg et al, 2013). Besides the polymorphs, a lot of crystallographic work has been carried out on mixtures of PZA with excipients or other APIs.…”

Section: Literature Data On the Phase Behavior Of Pyrazinamidementioning

confidence: 99%

“…Less clear is the observation that at very high loads, the enthalpy appears to curve slightly upwards, confirmed by both completely filled capsules and single crystal data. How this curvature comes about with powder samples could be explained by a combination of sublimation and disorder reported for the g form (Cherukuvada et al, 2010;Wahlberg et al, 2013). The melting temperature, which does not vary with sample mass, is much easier to determine.…”

Section: The Melting Equilibrium Of Form Gmentioning

confidence: 99%

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The phase relationship between the pyrazinamide polymorphs α and γ

Gbabode

Tamarit

et al. 2020

International Journal of Pharmaceutics

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Pyrazinamide is an active pharmaceutical compound for the treatment of tuberculosis. It possesses at least four crystalline polymorphs. Polymorphism may cause solubility problems as the case of ritonavir has clearly demonstrated; however, polymorphs also provide opportunities to improve pharmaceutical formulations, in particular if the stable form is not very soluble. The four polymorphs of pyrazinamide constitute a rich system to investigate the usefulness of metastable forms and their stabilization. However, despite the existence of a number of papers on the polymorphism of pyrazinamide, well-defined equilibrium conditions between the polymorphs appear to be lacking. This paper focusses on the phase behavior of the so-called a and g polymorphs of pyrazinamide, its liquid phase and vapor phase. The melting points and enthalpies of both solid phases have been determined. The equilibrium temperature between a and g was experimentally found at 392(1) K. Moreover, vapor pressures and solubilities of both phases have been determined, clearly indicating that form a is the more stable form at room temperature. High-pressure thermal analysis and the topological pressure-temperature phase diagram demonstrate that the g form is stabilized by pressure and becomes stable at room temperature under a pressure of 260 MPa. File list (2) download file view on ChemRxiv pyrazinamidePhaseBehavior-alpha-gamma-OA.pdf (1.93 MiB) download file view on ChemRxiv Supplementary Materials-OA.pdf (344.86 KiB)

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Section: P1 "mentioning

confidence: 99%

Section: Literature Data On the Phase Behavior Of Pyrazinamidementioning

confidence: 99%

Section: The Melting Equilibrium Of Form Gmentioning

confidence: 99%

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The phase relationship between the pyrazinamide polymorphs α and γ

Gbabode

Tamarit

et al. 2020

International Journal of Pharmaceutics

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“…Therefore, because the results of CSP are neglecting thermal motion and disorder, they should be compared with accurate structures from low-temperature measurements. 13 Subsequently, high temperature structures should be used in comparison with CSP methods that take entropy into account.…”

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confidence: 99%

A crystal structure prediction enigma solved: the gallic acid monohydrate system – surprises at 10 K

et al. 2017

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The seemingly unpredictable structure of gallic acid monohydrate form IV has been investigated using accurate X-ray diffraction measurements at temperatures of 10 and 123 K. The measurements demonstrate that the structure is commensurately modulated at 10 K and disordered at higher temperatures. Aided by charge-density modeling and periodic DFT calculations we show that the disorder gives a substantial stabilization of the structure.

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“…The results may thus provide guidance for the development of computational approaches to entropy estimation. We provide examples where the approach has been applied to the polymorphs of pyrazinamide, paracetamol [5], famotidine [6] and the epimeric xylitol and ribitol crystals [4,7], compare the experimental results to periodic DFT calculations [8,9] and discuss the merits and limitations of the approach as a tool for crystal structure prediction and crystal engineering. Multicomponent crystals with components present in a well-defined stoichiometric ratio (salts and co-crystals) attract much attention.…”

mentioning

confidence: 99%

Entropies from diffraction experiments: towards polymorph prediction

Madsen¹,

Wahlberg²,

Hope³

et al. 2012

Acta Cryst Sect A

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A central part of crystal structure prediction is to assess the relative stabilities of proposed structures. This is normally done by calculation of crystal energies or enthalpies (H). However it is well known that differences in entropies (S) can be sufficiently large to alter the order of stability of polymorphs with temperature (T), as expressed by the Gibbs equation G = H -TS. Indeed, in spite of recent success in prediction of crystal structures, polymorphs remain elusive [1].We demonstrate how differences in solid state entropies of polymorphic compounds can be obtained by analysis of the anisotropic displacement parameters derived from X-ray or neutron diffraction experiments [2][3][4]. This approach paves the way for understanding how molecular vibrations contribute to the stabilities of crystals. The results may thus provide guidance for the development of computational approaches to entropy estimation. We provide examples where the approach has been applied to the polymorphs of pyrazinamide, paracetamol [5], famotidine [6] and the epimeric xylitol and ribitol crystals [4,7], compare the experimental results to periodic DFT calculations [8,9] and discuss the merits and limitations of the approach as a tool for crystal structure prediction and crystal engineering. Multicomponent crystals with components present in a well-defined stoichiometric ratio (salts and co-crystals) attract much attention. Crystals of amino acids and their derivatives are of special interest for studies at non-ambient conditions due to the following reasons. First of all, studies of such compounds are interesting for improving our understanding of factors determining the formation of a crystal structure and its variations vs. temperature and pressure. Also they are promising as new materials, and the structure-forming units in these crystals are similar to those in the biopolymers and can be used as biomimetics.The main aim of this study was to compare the effect of increasing pressure and decreasing temperature on crystal structures of some selected derivatives of amino acids, that are bis(DL-serinium) oxalate dihydrate, DL-alaninium semi-oxalate monohydrate, and co-crystal of glycine with glutaric acid. A remarkable feature of these compounds is that very short O-H...O hydrogen bonds are present in the crystal structures.The properties of several types of H-bonds in bis(DL-serinium) oxalate dihydrate and DL-alaninium semi-oxalate monohydrate have been studied on cooling, and it was possible to correlate donor-acceptor distances with frequencies of OH stretching vibrations. The present study is a rare example when correlations between geometry and energy parameters have been found for selected individual H-bonds in the same crystalline compound at multiple temperatures. Originally, we supposed that a co-crystal -salt transition may be possible for co-crystal of glycine with glutaric acid, similarly to what has been observed for some other compounds, but real behavior of the system turned out to be quite unexpected and more compl...

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Polymorph Stability Prediction: On the Importance of Accurate Structures: A Case Study of Pyrazinamide

Cited by 20 publications

References 23 publications

The phase relationship between the pyrazinamide polymorphs α and γ

The phase relationship between the pyrazinamide polymorphs α and γ

A crystal structure prediction enigma solved: the gallic acid monohydrate system – surprises at 10 K

Entropies from diffraction experiments: towards polymorph prediction

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