Research Article

Quercetin-maleic acid co-crystal engineering using solvent evaporation to ıncrease quercetin solubility

Volume: 28 Number: 6 June 28, 2025
EN

Quercetin-maleic acid co-crystal engineering using solvent evaporation to ıncrease quercetin solubility

Abstract

This study aims to produce quercetin-maleic acid cocrystals with an increase in solubility properties. The preparation of quercetin-maleic acid cocrystal (CQAM) was carried out by solvent evaporation method using ethanol as a solvent. The quercetin-maleic acid cocrystal preparation was formed with two different stoichiometric ratios, namely quercetin-maleic acid (1:1 and 1:3). Solubility tests on quercetin-maleic acid cocrystals were carried out in 50 mL citrate buffer pH 5 at 37±0.5°C. The characterization tests used were DSC, PXRD, FTIR, and SEM, while for the evaluation, solubility tests were carried out. The results of DSC, PXRD, FTIR and SEM showed the formation of a new solid with the type of crystalline solid, so it was concluded as a cocrystalline solid. The results of the solubility test showed that the solubility value of quercetin-maleic acid cocrystal (1:1 and 1:3) was greater than that of pure quercetin. Solubility result of pure quercetin, CQAM 1:1 and CQAM 1:3 were 0.545 ± 0.0351 mg/L; 2.237 ± 0.0258 mg/L; and 6.352 ± 0.0258 mg/L, respectively. Quercetin–maleic acid cocrystals (1:1) and (1:3) experienced an increase in solubility of 4.11 and 11.65 times, respectively, from pure quercetin.

Keywords

References

  1. [1] Xu D, Hu MJ, Wang YQ, Cui YL. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules. 2019; 24(6): 1123. https://dx.doi.org/10.3390/molecules24061123.
  2. [2] Harwood MA. Critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic carcinogenic properties. Food Chem Toxicol. 2007; 45(11): 2179-205. https://dx.doi.org/10.1016/j.fct.2007.05.015.
  3. [3] Gao L, Liu G, Wang X, Liu F, Xu Y, and Ma J. Preparation of a chemically stable quercetin formulation using nanosuspension technology. Int JPharm. 2011; 404(1–2): 231–237. https://dx.doi.org/10.1016/j.ijpharm.2010.11.009.
  4. [4] Smith AJ, Kavuru P, Wojtas L, Zaworotko MJ, Shytle RD. Cocrystals of quercetin with improved solubility and oral bioavailability. Mol Pharmaceutics. 2011; 8(5): 1867–1876. https://dx.doi.org/10.1021/mp200209j.
  5. [5] Bruni G, Maietta M, Maggi L, Mustarelli P, Ferrara C, Berbenni V, Milanese C, Girella A, Marini A. Preparation and physicochemical characterization of acyclovir cocrystals with improved dissolution properties. J Pharm Sci. 2013; 102(11): 4079–4086. https://dx.doi.org/10.1002/jps.23721.
  6. [6] Krishnaiah YS. Pharmaceutical technologies for enhancing oral bioavailability of poorly soluble drugs. J Bioequiv Bioavailab. 2010; 2(2): 28–36. https://dx.doi.org/10.4172/jbb.1000027
  7. [7] Wisudyaningsih B, Sallama S, Siswandono, Setyawan D. The effect of pH and cocrystal quercetin-isonicotinamide on quercetin solubility and its thermodynamic. Res J Pharm Technol. 2021; 14(9): 4657–4661. https://dx.doi.org/10.52711/0974-360X.2021.00809.
  8. [8] Kakran M, Sahoo NG, Li L. Dissolution enhancement of quercetin through nanofabrication, complexation, and solid dispersion. Colloids Surf. B. 2011; 88(1): 121-130. https://dx.doi.org/10.1016/j.colsurfb.2011.06.020.

Details

Primary Language

English

Subjects

Pharmacy Management

Journal Section

Research Article

Publication Date

June 28, 2025

Submission Date

October 15, 2023

Acceptance Date

March 6, 2024

Published in Issue

Year 2024 Volume: 28 Number: 6

APA
Wisudyaningsih, B., Wicaksono, Y., & Herawati, E. (2025). Quercetin-maleic acid co-crystal engineering using solvent evaporation to ıncrease quercetin solubility. Journal of Research in Pharmacy, 28(6), 1982-1988. https://doi.org/10.29228/jrp.872
AMA
1.Wisudyaningsih B, Wicaksono Y, Herawati E. Quercetin-maleic acid co-crystal engineering using solvent evaporation to ıncrease quercetin solubility. J. Res. Pharm. 2025;28(6):1982-1988. doi:10.29228/jrp.872
Chicago
Wisudyaningsih, Budipratiwi, Yudi Wicaksono, and Elvina Herawati. 2025. “Quercetin-Maleic Acid Co-Crystal Engineering Using Solvent Evaporation to ıncrease Quercetin Solubility”. Journal of Research in Pharmacy 28 (6): 1982-88. https://doi.org/10.29228/jrp.872.
EndNote
Wisudyaningsih B, Wicaksono Y, Herawati E (July 1, 2025) Quercetin-maleic acid co-crystal engineering using solvent evaporation to ıncrease quercetin solubility. Journal of Research in Pharmacy 28 6 1982–1988.
IEEE
[1]B. Wisudyaningsih, Y. Wicaksono, and E. Herawati, “Quercetin-maleic acid co-crystal engineering using solvent evaporation to ıncrease quercetin solubility”, J. Res. Pharm., vol. 28, no. 6, pp. 1982–1988, July 2025, doi: 10.29228/jrp.872.
ISNAD
Wisudyaningsih, Budipratiwi - Wicaksono, Yudi - Herawati, Elvina. “Quercetin-Maleic Acid Co-Crystal Engineering Using Solvent Evaporation to ıncrease Quercetin Solubility”. Journal of Research in Pharmacy 28/6 (July 1, 2025): 1982-1988. https://doi.org/10.29228/jrp.872.
JAMA
1.Wisudyaningsih B, Wicaksono Y, Herawati E. Quercetin-maleic acid co-crystal engineering using solvent evaporation to ıncrease quercetin solubility. J. Res. Pharm. 2025;28:1982–1988.
MLA
Wisudyaningsih, Budipratiwi, et al. “Quercetin-Maleic Acid Co-Crystal Engineering Using Solvent Evaporation to ıncrease Quercetin Solubility”. Journal of Research in Pharmacy, vol. 28, no. 6, July 2025, pp. 1982-8, doi:10.29228/jrp.872.
Vancouver
1.Budipratiwi Wisudyaningsih, Yudi Wicaksono, Elvina Herawati. Quercetin-maleic acid co-crystal engineering using solvent evaporation to ıncrease quercetin solubility. J. Res. Pharm. 2025 Jul. 1;28(6):1982-8. doi:10.29228/jrp.872

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