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Inhibition of the Vapor-Mediated Phase Transition of the High Temperature Form of Pyrazinamide

[Image: see text] Tailor-made additives can prove an effective method to prolong the lifetime of metastable forms of pharmaceutical compounds by surface stabilization. Pyrazinamide (PZA) is a pharmaceutical compound with four polymorphic forms. The high temperature γ form, which can be produced by s...

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Autores principales: Smets, M. M. H., Baaklini, G., Tijink, A., Sweers, L., Vossen, C. H. F., Brandel, C., Meekes, H., Cuppen, H. M., Coquerel, G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806087/
https://www.ncbi.nlm.nih.gov/pubmed/29445318
http://dx.doi.org/10.1021/acs.cgd.7b01550
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author Smets, M. M. H.
Baaklini, G.
Tijink, A.
Sweers, L.
Vossen, C. H. F.
Brandel, C.
Meekes, H.
Cuppen, H. M.
Coquerel, G.
author_facet Smets, M. M. H.
Baaklini, G.
Tijink, A.
Sweers, L.
Vossen, C. H. F.
Brandel, C.
Meekes, H.
Cuppen, H. M.
Coquerel, G.
author_sort Smets, M. M. H.
collection PubMed
description [Image: see text] Tailor-made additives can prove an effective method to prolong the lifetime of metastable forms of pharmaceutical compounds by surface stabilization. Pyrazinamide (PZA) is a pharmaceutical compound with four polymorphic forms. The high temperature γ form, which can be produced by spray drying or sublimation growth, is metastable at room temperature and transforms within days when produced by spray drying, and within several months up to years for single crystals produced by sublimation. However, when PZA is cospray dried with 1,3-dimethylurea (DMU), it has been reported to remain in its γ form for several years. Scanning electron microscopy (SEM) images reveal that the phase transition from γ-PZA to the low temperature forms involves a vapor-mediated recrystallization, while the reverse phase transition upon heating is a nucleation-and-growth solid–solid phase transition. The lifetime-extending effect of DMU on spray-dried PZA has been investigated in more detail and compared with high-energy ball milling of sublimation-grown γ-PZA crystals. Co-ball milling of PZA and DMU is found to extend the lifetime of the high temperature form of PZA to a few months, while separate ball milling leads to an extension of merely a few weeks. DMU acts as an additive that most likely stabilizes the surface of γ-PZA, which would reduce the vapor pressure of PZA, thereby reducing the transition rate. Alternatively, DMU could prevent nucleation of low temperature forms of PZA.
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spelling pubmed-58060872018-02-12 Inhibition of the Vapor-Mediated Phase Transition of the High Temperature Form of Pyrazinamide Smets, M. M. H. Baaklini, G. Tijink, A. Sweers, L. Vossen, C. H. F. Brandel, C. Meekes, H. Cuppen, H. M. Coquerel, G. Cryst Growth Des [Image: see text] Tailor-made additives can prove an effective method to prolong the lifetime of metastable forms of pharmaceutical compounds by surface stabilization. Pyrazinamide (PZA) is a pharmaceutical compound with four polymorphic forms. The high temperature γ form, which can be produced by spray drying or sublimation growth, is metastable at room temperature and transforms within days when produced by spray drying, and within several months up to years for single crystals produced by sublimation. However, when PZA is cospray dried with 1,3-dimethylurea (DMU), it has been reported to remain in its γ form for several years. Scanning electron microscopy (SEM) images reveal that the phase transition from γ-PZA to the low temperature forms involves a vapor-mediated recrystallization, while the reverse phase transition upon heating is a nucleation-and-growth solid–solid phase transition. The lifetime-extending effect of DMU on spray-dried PZA has been investigated in more detail and compared with high-energy ball milling of sublimation-grown γ-PZA crystals. Co-ball milling of PZA and DMU is found to extend the lifetime of the high temperature form of PZA to a few months, while separate ball milling leads to an extension of merely a few weeks. DMU acts as an additive that most likely stabilizes the surface of γ-PZA, which would reduce the vapor pressure of PZA, thereby reducing the transition rate. Alternatively, DMU could prevent nucleation of low temperature forms of PZA. American Chemical Society 2017-12-28 2018-02-07 /pmc/articles/PMC5806087/ /pubmed/29445318 http://dx.doi.org/10.1021/acs.cgd.7b01550 Text en Copyright © 2017 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
spellingShingle Smets, M. M. H.
Baaklini, G.
Tijink, A.
Sweers, L.
Vossen, C. H. F.
Brandel, C.
Meekes, H.
Cuppen, H. M.
Coquerel, G.
Inhibition of the Vapor-Mediated Phase Transition of the High Temperature Form of Pyrazinamide
title Inhibition of the Vapor-Mediated Phase Transition of the High Temperature Form of Pyrazinamide
title_full Inhibition of the Vapor-Mediated Phase Transition of the High Temperature Form of Pyrazinamide
title_fullStr Inhibition of the Vapor-Mediated Phase Transition of the High Temperature Form of Pyrazinamide
title_full_unstemmed Inhibition of the Vapor-Mediated Phase Transition of the High Temperature Form of Pyrazinamide
title_short Inhibition of the Vapor-Mediated Phase Transition of the High Temperature Form of Pyrazinamide
title_sort inhibition of the vapor-mediated phase transition of the high temperature form of pyrazinamide
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806087/
https://www.ncbi.nlm.nih.gov/pubmed/29445318
http://dx.doi.org/10.1021/acs.cgd.7b01550
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