Anti-solvent co-crystallization of carbamazepine and saccharin

In Chun Wang, Min Jeong Lee, Sang Jun Sim, Woo Sik Kim, Nan Hee Chun, Guang J. Choi

Research output: Contribution to journalArticle

35 Citations (Scopus)

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. Co-crystallization 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.

Original languageEnglish
Pages (from-to)311-322
Number of pages12
JournalInternational Journal of Pharmaceutics
Volume450
Issue number1-2
DOIs
Publication statusPublished - 2013 Jun 25

Fingerprint

Saccharin
Carbamazepine
Crystallization
Methanol
Water
Powders
Fourier Transform Infrared Spectroscopy
Hydrogen Bonding
Hydrogen
Temperature
Pharmaceutical Preparations

Keywords

  • Anti-solvent crystallization
  • ATR-FTIR
  • Carbamazepine
  • Co-crystal
  • Hydrogen bonding
  • Saccharin

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Anti-solvent co-crystallization of carbamazepine and saccharin. / Wang, In Chun; Lee, Min Jeong; Sim, Sang Jun; Kim, Woo Sik; Chun, Nan Hee; Choi, Guang J.

In: International Journal of Pharmaceutics, Vol. 450, No. 1-2, 25.06.2013, p. 311-322.

Research output: Contribution to journalArticle

Wang, In Chun ; Lee, Min Jeong ; Sim, Sang Jun ; Kim, Woo Sik ; Chun, Nan Hee ; Choi, Guang J. / Anti-solvent co-crystallization of carbamazepine and saccharin. In: International Journal of Pharmaceutics. 2013 ; Vol. 450, No. 1-2. pp. 311-322.
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AU - Choi, Guang J.

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