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Controlling the Polymorphism of Indomethacin with Poloxamer 407 in a Gas Antisolvent Crystallization Process

[Image: see text] The polymorphic control of active pharmaceutical ingredients (APIs) is a major challenge in the manufacture of medicines. Crystallization methods that use supercritical carbon dioxide as an antisolvent can create unique solid forms of APIs, with a particular tendency to generate me...

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Autores principales: Cañellas, Fidel Méndez, Verma, Vivek, Kujawski, Jacek, Geertman, Robert, Tajber, Lidia, Padrela, Luis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730483/
https://www.ncbi.nlm.nih.gov/pubmed/36506150
http://dx.doi.org/10.1021/acsomega.2c05259
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author Cañellas, Fidel Méndez
Verma, Vivek
Kujawski, Jacek
Geertman, Robert
Tajber, Lidia
Padrela, Luis
author_facet Cañellas, Fidel Méndez
Verma, Vivek
Kujawski, Jacek
Geertman, Robert
Tajber, Lidia
Padrela, Luis
author_sort Cañellas, Fidel Méndez
collection PubMed
description [Image: see text] The polymorphic control of active pharmaceutical ingredients (APIs) is a major challenge in the manufacture of medicines. Crystallization methods that use supercritical carbon dioxide as an antisolvent can create unique solid forms of APIs, with a particular tendency to generate metastable polymorphic forms. In this work, the effects of processing conditions within a gas antisolvent (GAS) crystallization method, such as pressure, stirring rate, and temperature, as well as the type of solvent used and the presence of an additive, on the polymorphism of indomethacin were studied. Consistent formation of the X-ray powder diffraction-pure α polymorphic form of indomethacin by GAS was only achieved when a polymer, poloxamer 407, was used as an additive. Using the GAS method in combination with poloxamer 407 as a molecular additive enabled full control over the polymorphic form of indomethacin, regardless of the processing conditions employed, such as pressure, temperature, stirring rate, and type of solvent. A detailed molecular modeling study provided insight into the role of poloxamer 407 in the polymorphic outcome of indomethacin and concluded that it favored the formation of the α polymorph.
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spelling pubmed-97304832022-12-09 Controlling the Polymorphism of Indomethacin with Poloxamer 407 in a Gas Antisolvent Crystallization Process Cañellas, Fidel Méndez Verma, Vivek Kujawski, Jacek Geertman, Robert Tajber, Lidia Padrela, Luis ACS Omega [Image: see text] The polymorphic control of active pharmaceutical ingredients (APIs) is a major challenge in the manufacture of medicines. Crystallization methods that use supercritical carbon dioxide as an antisolvent can create unique solid forms of APIs, with a particular tendency to generate metastable polymorphic forms. In this work, the effects of processing conditions within a gas antisolvent (GAS) crystallization method, such as pressure, stirring rate, and temperature, as well as the type of solvent used and the presence of an additive, on the polymorphism of indomethacin were studied. Consistent formation of the X-ray powder diffraction-pure α polymorphic form of indomethacin by GAS was only achieved when a polymer, poloxamer 407, was used as an additive. Using the GAS method in combination with poloxamer 407 as a molecular additive enabled full control over the polymorphic form of indomethacin, regardless of the processing conditions employed, such as pressure, temperature, stirring rate, and type of solvent. A detailed molecular modeling study provided insight into the role of poloxamer 407 in the polymorphic outcome of indomethacin and concluded that it favored the formation of the α polymorph. American Chemical Society 2022-11-18 /pmc/articles/PMC9730483/ /pubmed/36506150 http://dx.doi.org/10.1021/acsomega.2c05259 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Cañellas, Fidel Méndez
Verma, Vivek
Kujawski, Jacek
Geertman, Robert
Tajber, Lidia
Padrela, Luis
Controlling the Polymorphism of Indomethacin with Poloxamer 407 in a Gas Antisolvent Crystallization Process
title Controlling the Polymorphism of Indomethacin with Poloxamer 407 in a Gas Antisolvent Crystallization Process
title_full Controlling the Polymorphism of Indomethacin with Poloxamer 407 in a Gas Antisolvent Crystallization Process
title_fullStr Controlling the Polymorphism of Indomethacin with Poloxamer 407 in a Gas Antisolvent Crystallization Process
title_full_unstemmed Controlling the Polymorphism of Indomethacin with Poloxamer 407 in a Gas Antisolvent Crystallization Process
title_short Controlling the Polymorphism of Indomethacin with Poloxamer 407 in a Gas Antisolvent Crystallization Process
title_sort controlling the polymorphism of indomethacin with poloxamer 407 in a gas antisolvent crystallization process
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730483/
https://www.ncbi.nlm.nih.gov/pubmed/36506150
http://dx.doi.org/10.1021/acsomega.2c05259
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