Journal article
Assessing Structures and Solution Behaviors of Molecular and Ionic Cocrystals with a Common Bioactive Molecule: 2,4-Pyridinedicarboxylic Acid with Tranexamic Acid and Nicotinamide
Crystal growth & design, Vol.24(16), pp.6618-6624
08/21/2024
DOI: 10.1021/acs.cgd.4c00525
PMCID: PMC11342296
PMID: 39185356
Appears in UI Libraries Support Open Access
Abstract
Cocrystals of 2,4-pyridinedicarboxylic acid (PDA) with either nicotinamide (NTD) or tranexamic acid (TXA) as (PDA)·(NTD) and 2(PDA)·(TXA), respectively, are reported, with the former being a molecular cocrystal and the latter being an ionic cocrystal. Single-crystal structure analyses showed that PDA and its coformers are sustained by neutral and ionic hydrogen bonds. Suspensions of (PDA)·(NTD) resulted in complete conversion to PDA monohydrate after 48 h, while 2(PDA)·(TXA) was thermodynamically stable at a lower pH and showed a 2-fold increase in the PDA concentration, relative to pure PDA monohydrate under similar conditions. Thermal characterization of 2(PDA)·(TXA) displayed a lower melting point and a lower heat of fusion, relative to the pure components. Powder dissolution studies were evaluated for PDA, (PDA)·(NTD), and 2(PDA)·(TXA) and the corresponding physical mixtures. The percent of PDA dissolved rapidly reached near 100% for most cases; however, for 2(PDA)·(TXA), complete dissolution was not achieved, and the amount of PDA dissolved decreased to 85% after 3 h. Instability of 2(PDA)·(TXA) was likely a result of a high solution pH during dissolution, and our results confirm that the solution pH plays a key role in determining the solution behavior and phase stability of the cocrystals.
Details
- Title: Subtitle
- Assessing Structures and Solution Behaviors of Molecular and Ionic Cocrystals with a Common Bioactive Molecule: 2,4-Pyridinedicarboxylic Acid with Tranexamic Acid and Nicotinamide
- Creators
- Charles Izuchukwu Ezekiel - University of IowaSanika Jadhav - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, United StatesLewis L. Stevens - University of Iowa, Pharmaceutical Sciences and Experimental TherapeuticsLeonard R. MacGillivray - University of Iowa, Chemistry
- Resource Type
- Journal article
- Publication Details
- Crystal growth & design, Vol.24(16), pp.6618-6624
- Publisher
- American Chemical Society
- DOI
- 10.1021/acs.cgd.4c00525
- PMID
- 39185356
- PMCID
- PMC11342296
- ISSN
- 1528-7483
- eISSN
- 1528-7505
- Language
- English
- Electronic publication date
- 08/01/2024
- Date published
- 08/21/2024
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Chemistry
- Record Identifier
- 9984695158602771
Metrics
25 Record Views