Crystallization from the Gas Phase: Morphology Control, Co-Crystal and Salt Formation †
Abstract
:1. Introduction
2. Experiments
2.1. Crystallisation from the Gas Phase and Crystal Structure Determination and Refinement
2.2. Ball Milling
2.3. Solution Crystallisation
3. Results
3.1. Pyrimethamine Co-Crystal Screening
3.2. Diflunisal Co-Crystal Screening
3.3. Morphology Control in the Gas Phase Using Tailor Made Additives
4. Discussion
4.1. Methods of Co-Crystallisation
4.2. Co-Crystallisation of Pyrimethamine
4.3. Co-Crystallisation of Diflunisal
4.4. Morphology Control in the Gas Phase
4.5. Modelling Hydrogen Transfer in the Gas Phase
5. Conclusions
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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No. | Components | Solvent Used | Solvate | Note |
---|---|---|---|---|
1 | Pyrimethamine/Benzoic acid | Methanol | Water | |
2 | Pyrimethamine/Benzoic acid/Succinimide | Methanol | - | |
3 | Pyrimethamine/Nicotinic acid | Methanol | Water | |
4 | Pyrimethanime/Saccharin | Methanol | Water | H2O solvate I |
5 | Pyimethamine/Saccharin | Methanol | Water | H2O solvate II |
6 | Pyrimethamine/Saccharin | Methanol | - | Polymorph II |
7 | Pyrimethamine/Saccharin | Methanol | Methanol | |
8 | Pyrimethamine/Saccharin | Acetonitrile | Acetonitrile | |
9 | Pyrimethamine/Sorbic acid | Methanol | - | |
10 | Pyrimethamine/Saccharin/ Sorbic acid | Methanol | - | |
11 | Pyrimethamine/Mandelic acid | Methanol | - | |
12 | Pyrimethamine/Saccharin/Glutarimide | Methanol | - | |
13 | Pyrimethamine/Anthranillic acid | Acetonitrile | Water | |
14 | Pyrimethamine | Acetonitrile | Acetonitrile | |
15 | Pyrimethamine/Isonicotinic acid | Acetonitrile | Water |
Components | Amount API (mg) | Amount Co-Former (mg) | Temperature API (°C) | Temperature Co-Former (°C) | Time (hr) |
---|---|---|---|---|---|
DIF/INA | 50 of milled sample (DIF 250.2 + INA 122.1 + BEN 37.2) | Heater 1 170.1 Heater 2 160.5 | 2 | ||
DIF/EBIPY | 25 | 9.1 | 180.0 | 140 | 2 |
DIF/BIPY | 50 | 15.6 | 193.0 | 126.3 | 2 |
DIF/PBIPY | 50 | 39.62 | 174.4 | 50.0 | 12 |
DIF/PIP | 50 | 17.2 | 196.4 | 61.8 | 12 |
DIF/DMAP | 50 | 24.62 | 161.4 | 69.2 | 4 |
Components | Additive | Co-Crystal |
---|---|---|
BZA/INA | - | 1:1 needles |
BZA/INA | BEN | 1:1 blocks |
BZA/INA | - | 2:1 plates |
DIF/INA | - | 2:1 fibers |
DIF/INA | BEN | 2:1 needles |
DIF/BIPY | - | 2:1 needles |
DIF/EBIPY | - | 2:1 thin plates |
DIF/EBIPY | SPY | 2:1 needles |
Compound | pKa | Difference (Base-DIF) | Outcome |
---|---|---|---|
Diflunisal | 2.94 | 0 | - |
BIPY | 3.39 | 0.33 | Co-crystal |
INA | 3.39 | 0.45 | Co-crystal |
EBipy | 5.5 | 2.56 | Co-crystal |
PBipy | 6.3 | 3.36 | Salt |
DMAP | 9.7 | 6.76 | Salt |
Piperazine | 9.83 | 6.89 | Salt |
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O’Malley, C.; McArdle, P.; Erxleben, A. Crystallization from the Gas Phase: Morphology Control, Co-Crystal and Salt Formation. Proceedings 2021, 78, 1. https://doi.org/10.3390/IECP2020-08797
O’Malley C, McArdle P, Erxleben A. Crystallization from the Gas Phase: Morphology Control, Co-Crystal and Salt Formation. Proceedings. 2021; 78(1):1. https://doi.org/10.3390/IECP2020-08797
Chicago/Turabian StyleO’Malley, Ciaran, Patrick McArdle, and Andrea Erxleben. 2021. "Crystallization from the Gas Phase: Morphology Control, Co-Crystal and Salt Formation" Proceedings 78, no. 1: 1. https://doi.org/10.3390/IECP2020-08797