A Novel Cocrystal of Daidzein with Piperazine to Optimize the Solubility, Permeability and Bioavailability of Daidzein
Abstract
:1. Introduction
2. Results and Discussion
2.1. Crystal Structure Analysis
2.2. PXRD Analysis
2.3. IR Analysis
2.4. Thermal Analysis
2.5. Stability Study
2.6. Solubility and Powder Dissolution In Vitro
2.7. Permeability Study
2.8. Pharmacokinetics In Vivo
3. Materials and Methods
3.1. Materials
3.2. Preparation of DAI-PPZ Cocrystal
3.3. Preparation of Single Crystal
3.4. SCXRD Analysis
3.5. MEPS Calculations
3.6. PXRD Analysis
3.7. IR Analysis
3.8. Thermal Analysis
3.9. Stability Evaluation
3.10. Solubility Determination and PH Measurement
3.11. Powder Dissolution In Vitro
3.12. Flux Measurements
3.13. Pharmacokinetic Study In Vivo
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameters | Daidzein–Piperazine Cocrystal |
---|---|
Empirical formula | C19H20N2O4 |
Formula weight | 340.37 |
Crystal size/mm | 0.22 × 0.18 × 0.12 |
Description | block |
Crystal system | Monoclinic |
Space group | P21/C |
a (Å) | 12.162(1) |
b (Å) | 6.385(1) |
c (Å) | 21.224(1) |
β (◦) | 95.02(1) |
Volume (Å3) | 1641.9(1) |
Z | 4 |
Completeness | 99.7% |
Density (g·cm−3) | 1.377 |
Reflections with I > 2σ (I) | 2792 |
Rindexs (I > 2σI) | R1 = 0.0556, wR2 = 0.1578 |
Goodness of fit on F2 | 1.035 |
CCDC deposition number | 2313133 |
D–H⋯A | d(D⋯A) (Å) | ∠(DHA) (deg) | Symmetry Code |
---|---|---|---|
O4−H4⋯N2P | 2.738 | 146.91 | - |
O3−H3⋯N1P | 2.557 | 131.51 | [x + 1, −y + 1/2, z − 1/2] |
N1P−H1P⋯O2 | 2.919 | 127.93 | [−x, −y + 1, −z + 1] |
N2P−H2P⋯O3 | 3.092 | 175.17 | [−x + 1, −y + 1, −z + 1] |
Compound | PH 1.2 | PH 4.5 | PH 6.8 | PH 7.0 |
---|---|---|---|---|
DAI | 1.31 ± 0.06 | 4.72 ± 0.01 | 6.80 ± 0.04 | 6.62 ± 0.57 |
DAI-PPZ | 1.80 ± 0.35 | 4.86 ± 0.01 | 7.23 ± 0.05 | 9.67 ± 0.21 |
PM | 1.88 ± 0.01 | 4.82 ± 0.02 | 7.18 ± 0.07 | 9.70 ± 0.17 |
Parameter | Daidzein | Daidzein-Piperazine |
---|---|---|
AUC(0–t) (µg/L·h) | 798.15 ± 398.10 | 2600.55 ± 701.41 ** |
AUC(0–∞) (µg/L·h) | 895.53 ± 388.94 | 2824.12 ± 764.66 ** |
MRT(0–t) (h) | 7.89 ± 1.04 | 9.79 ± 1.14 * |
MRT(0–∞) (h) | 12.29 ± 5.50 | 11.61 ± 3.04 |
t1/2z (h) | 8.58 ± 6.16 | 4.76 ± 2.18 |
Tmax (h) | 3.75 ± 2.89 | 8.17 ± 2.71 * |
CLz/F (L/h/kg) | 128.09 ± 47.35 | 50.57 ± 14.12 ** |
Cmax (µg/L) | 131.50 ± 74.29 | 268.47 ± 45.73 ** |
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Wang, Z.; Li, S.; Li, Q.; Wang, W.; Liu, M.; Yang, S.; Zhang, L.; Yang, D.; Du, G.; Lu, Y. A Novel Cocrystal of Daidzein with Piperazine to Optimize the Solubility, Permeability and Bioavailability of Daidzein. Molecules 2024, 29, 1710. https://doi.org/10.3390/molecules29081710
Wang Z, Li S, Li Q, Wang W, Liu M, Yang S, Zhang L, Yang D, Du G, Lu Y. A Novel Cocrystal of Daidzein with Piperazine to Optimize the Solubility, Permeability and Bioavailability of Daidzein. Molecules. 2024; 29(8):1710. https://doi.org/10.3390/molecules29081710
Chicago/Turabian StyleWang, Zhipeng, Shuang Li, Qi Li, Wenwen Wang, Meiru Liu, Shiying Yang, Li Zhang, Dezhi Yang, Guanhua Du, and Yang Lu. 2024. "A Novel Cocrystal of Daidzein with Piperazine to Optimize the Solubility, Permeability and Bioavailability of Daidzein" Molecules 29, no. 8: 1710. https://doi.org/10.3390/molecules29081710
APA StyleWang, Z., Li, S., Li, Q., Wang, W., Liu, M., Yang, S., Zhang, L., Yang, D., Du, G., & Lu, Y. (2024). A Novel Cocrystal of Daidzein with Piperazine to Optimize the Solubility, Permeability and Bioavailability of Daidzein. Molecules, 29(8), 1710. https://doi.org/10.3390/molecules29081710