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Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients

Multicomponent solid forms of active pharmaceutical ingredients represent a modern method of tuning their physicochemical properties. Typically, salts are the most commonly used multicomponent solid form in the pharmaceutical industry. More than 38% are formulated as organic cations. Salt screening...

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Autores principales: Babor, Martin, Nievergelt, Philipp P., Čejka, Jan, Zvoníček, Vít, Spingler, Bernhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327184/
https://www.ncbi.nlm.nih.gov/pubmed/30713712
http://dx.doi.org/10.1107/S2052252518017876
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author Babor, Martin
Nievergelt, Philipp P.
Čejka, Jan
Zvoníček, Vít
Spingler, Bernhard
author_facet Babor, Martin
Nievergelt, Philipp P.
Čejka, Jan
Zvoníček, Vít
Spingler, Bernhard
author_sort Babor, Martin
collection PubMed
description Multicomponent solid forms of active pharmaceutical ingredients represent a modern method of tuning their physicochemical properties. Typically, salts are the most commonly used multicomponent solid form in the pharmaceutical industry. More than 38% are formulated as organic cations. Salt screening is an essential but demanding step when identifying the most appropriate formulation. The microbatch under-oil crystallization technique of proteins has been combined with the previously developed high-throughput vapour-diffusion screening for use as a novel method of primary salt screening of organic cations. The procedure allows the set up of about 100 crystallization experiments per 30 min. This requires between 17 and 564 mg of screened cationic active pharmaceutical ingredients, which were of moderate to very high water solublity. Five distinct organic salts, three of them diverse active pharmaceutical compounds or the other enantiomer thereof, in the form of chloride salts were tested. The screening was extremely successful; at least two new single-crystal structures could be obtained for each particular compound and many more salts as single crystals were formed compared with our previous vapour-diffusion method.
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spelling pubmed-63271842019-02-01 Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients Babor, Martin Nievergelt, Philipp P. Čejka, Jan Zvoníček, Vít Spingler, Bernhard IUCrJ Research Papers Multicomponent solid forms of active pharmaceutical ingredients represent a modern method of tuning their physicochemical properties. Typically, salts are the most commonly used multicomponent solid form in the pharmaceutical industry. More than 38% are formulated as organic cations. Salt screening is an essential but demanding step when identifying the most appropriate formulation. The microbatch under-oil crystallization technique of proteins has been combined with the previously developed high-throughput vapour-diffusion screening for use as a novel method of primary salt screening of organic cations. The procedure allows the set up of about 100 crystallization experiments per 30 min. This requires between 17 and 564 mg of screened cationic active pharmaceutical ingredients, which were of moderate to very high water solublity. Five distinct organic salts, three of them diverse active pharmaceutical compounds or the other enantiomer thereof, in the form of chloride salts were tested. The screening was extremely successful; at least two new single-crystal structures could be obtained for each particular compound and many more salts as single crystals were formed compared with our previous vapour-diffusion method. International Union of Crystallography 2019-01-01 /pmc/articles/PMC6327184/ /pubmed/30713712 http://dx.doi.org/10.1107/S2052252518017876 Text en © Martin Babor et al. 2019 http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/4.0/
spellingShingle Research Papers
Babor, Martin
Nievergelt, Philipp P.
Čejka, Jan
Zvoníček, Vít
Spingler, Bernhard
Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients
title Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients
title_full Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients
title_fullStr Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients
title_full_unstemmed Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients
title_short Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients
title_sort microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327184/
https://www.ncbi.nlm.nih.gov/pubmed/30713712
http://dx.doi.org/10.1107/S2052252518017876
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