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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2019
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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. |
format | Online Article Text |
id | pubmed-6327184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
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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