Abstract
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 language | English |
|---|---|
| Pages (from-to) | 3807-3814 |
| Number of pages | 8 |
| Journal | Crystal Growth and Design |
| Volume | 19 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2019 Jun 10 |
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ASJC Scopus subject areas
- Chemistry(all)
- Materials Science(all)
- Condensed Matter Physics
Cite this
Cocrystal Formation via Resorcinol-Urea Interactions : Naringenin and Carbamazepine. / Lee, Cheongcheon; Cho, A. Young; Yoon, Woojin; Yun, Hoseop; Kang, Jeong Won; Lee, Jonghwi.
In: Crystal Growth and Design, Vol. 19, No. 7, 10.06.2019, p. 3807-3814.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cocrystal Formation via Resorcinol-Urea Interactions
T2 - Naringenin and Carbamazepine
AU - Lee, Cheongcheon
AU - Cho, A. Young
AU - Yoon, Woojin
AU - Yun, Hoseop
AU - Kang, Jeong Won
AU - Lee, Jonghwi
PY - 2019/6/10
Y1 - 2019/6/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85069894701&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069894701&partnerID=8YFLogxK
U2 - 10.1021/acs.cgd.9b00269
DO - 10.1021/acs.cgd.9b00269
M3 - Article
AN - SCOPUS:85069894701
VL - 19
SP - 3807
EP - 3814
JO - Crystal Growth and Design
JF - Crystal Growth and Design
SN - 1528-7483
IS - 7
ER -