Journal article
The Effects of Humidity on Spontaneous Cocrystallization: A Survey of Diacid Cocrystals with Caffeine, Theophylline, and Nicotinamide
Journal of chemical crystallography, Vol.52(4), pp.479-484
12/01/2022
DOI: 10.1007/s10870-022-00922-8
Abstract
Pharmaceutical cocrystals comprise one active pharmaceutical ingredient (API) and at least one small molecule excipient coformer. While solvent evaporation and mechanochemistry are the preferred methods for their synthesis, some cocrystals are known to form spontaneously at ambient conditions when powders of input materials are mixed-a process not yet fully understood. Aqueous humidity is also known to accelerate spontaneous cocrystal formation. We report here the extent of spontaneous cocrystallization for 14 cocrystal systems, at four levels of humidity. The binary cocrystals in our study consist of a model API (caffeine, theophylline, nicotinamide) and a small chain diacid coformer (oxalic acid, malonic acid, maleic acid, fumaric acid, succinic acid, glutaric acid). The spontaneous cocrystal formation was monitored ex situ by powder X-ray diffraction over several weeks. Our results show cocrystal formation in all 14 systems to varying extent and are consistent with literature reports that higher humidity correlates with more rapid cocrystal formation. We find that cocrystals containing smaller coformers often form faster. Based on our findings, we identify several cocrystals as candidates for future study.
Details
- Title: Subtitle
- The Effects of Humidity on Spontaneous Cocrystallization: A Survey of Diacid Cocrystals with Caffeine, Theophylline, and Nicotinamide
- Creators
- Riley D. Davies - Oberlin CollegeNicolas J. Vigilante - Oberlin CollegeAaron D. Frederick - Oberlin CollegeVenkata S. Mandala - Oberlin CollegeManish A. Mehta - Oberlin College
- Resource Type
- Journal article
- Publication Details
- Journal of chemical crystallography, Vol.52(4), pp.479-484
- DOI
- 10.1007/s10870-022-00922-8
- ISSN
- 1074-1542
- eISSN
- 1572-8854
- Publisher
- Springer Nature
- Number of pages
- 6
- Grant note
- Oberlin College DMR-0922588 / National Science Foundation, MRI; National Science Foundation (NSF) CHE-1464948; CHE-2100582 / National Science Foundation, RUI; National Science Foundation (NSF)
- Language
- English
- Date published
- 12/01/2022
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9985112883302771
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