Cocrystal Formation via Resorcinol-Urea Interactions: Naringenin and Carbamazepine

Cheongcheon Lee, A. Young Cho, Woojin Yoon, Hoseop Yun, Jeong Won Kang, Jonghwi Lee

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Improving the stability, bioavailability, and processability of active pharmaceutical ingredients (APIs) has been the key research goal in the field of pharmaceutical crystallization. Cocrystallization has been considered as an effective route to achieve this goal, and intense research over decades has revealed cocrystals of many APIs. However, most cocrystal formers have been designed based primarily on their molecular interactions not their health benefits. Herein, we choose naringenin (N), a natural flavonoid, as a novel cocrystal former as it has many health efficacies and the ability to form specific interactions. At a 1:1 stoichiometric ratio, N successfully forms a cocrystal with carbamazepine (CBZ), whose plasma concentration is known to be improved by natural flavonoids such as N. The resorcinol functional group of N and the urea functional group of CBZ are connected through hydrogen bonds, and the improved stability of the cocrystal seems to originate from this structure. The melting temperature of the cocrystal is 262 °C, which is higher than those of CBZ and N, and the better stability of the cocrystal is further confirmed by the observation of enhanced hydration stability (up to 30 days at 93% RH). This novel strategy of cocrystallization using natural flavonoids could improve the commercialization potential of API cocrystals.

Original languageEnglish
Pages (from-to)3807-3814
Number of pages8
JournalCrystal Growth and Design
Issue number7
Publication statusPublished - 2019 Jun 10

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation grant from the Korean Ministry of Science, ICT, and Future Planning (Engineering Research Center 2014R1A5A1009799).

Publisher Copyright:
© 2019 American Chemical Society.

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics


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