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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 (2019). Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients. IU Cr J, 6(1):145-151.

Abstract

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.

Abstract

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:1 January 2019
Deposited On:24 Jan 2019 15:24
Last Modified:04 Feb 2019 14:33
Publisher:International Union of Crystallography
ISSN:2052-2525
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1107/s2052252518017876
Project Information:
  • : FunderSNSF
  • : Grant ID206021_164018
  • : Project TitleDual X-ray Wavelength Single-Crystal Diffractometer
  • : FunderCzech Science Foundation
  • : Grant ID16-10035S
  • : Project Title
  • : FunderSpecific University Research
  • : Grant ID21-SVV/2018
  • : Project Title

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