Anti-solvent co-crystallization of carbamazepine and saccharin
- Authors
- Wang, In-Chun; Lee, Min-Jeong; Sim, Sang-Jun; Kim, Woo-Sik; Chun, Nan-Hee; Choi, Guang J.
- Issue Date
- 25-6월-2013
- Publisher
- ELSEVIER
- Keywords
- Co-crystal; Carbamazepine Saccharin Anti; solvent crystallization; ATR; FTIR; Hydrogen bonding
- Citation
- INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.450, no.1-2, pp.311 - 322
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF PHARMACEUTICS
- Volume
- 450
- Number
- 1-2
- Start Page
- 311
- End Page
- 322
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/102940
- DOI
- 10.1016/j.ijpharm.2013.04.012
- ISSN
- 0378-5173
- Abstract
- The co-crystal approach has been investigated extensively over the past decade as one of the most promising methods to enhance the dissolution properties of insoluble drug substances. Co-crystal powders are typically produced by mechanical grinding (neat or wet) or a solution method (evaporation or cooling). In this study, high-purity carbamazepine-saccharin (CBZ-SAC) co-crystals were manufactured by a novel method, anti-solvent addition. Among various solvents, methanol was found to perform well with water as the anti-solvent for the co-crystallization of CBZ and SAC. When water was added to the methanol solution of CBZ and SAC at room temperature under agitation, nucleation of CBZ-SAC co-crystals occurred within 2-3 min. Cocrystallization was complete after 30 min, giving a solid yield as high as 84.5% on a CBZ basis. The effects of initial concentrations, focusing on the SAC/ CBZ ratio, were examined to establish optimal conditions. The whole anti-solvent co-crystallization process was monitored at-line via ATR-FTIR analysis of regularly sampled solutions. The nucleation and crystal growth of CBZ-SAC co-crystals were detected by a significant increase in absorption in the range of 2400-2260 cm(-1), associated with the formation of hydrogen bonds between the carbonyl group in CBZ and the N-H of SAC. When CBZ hydrates were formed as impurities during anti-solvent co-crystallization, the hydrogen bonding between methanol and water was reduced greatly, primarily due to the incorporation of water molecules into the CBZ crystal lattice. In conclusion, an anti-solvent approach can be used to produce highly pure CBZ-SAC co-crystal powders with a high solid yield. (C) 2013 Elsevier B. V. All rights reserved.
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