Budipratiwi Wisudyaningsih, Solihatus Sallama, Siswandono, Dwi Setyawan
Budipratiwi Wisudyaningsih1, Solihatus Sallama1, Siswandono2, Dwi Setyawan2*
1Faculty of Pharmacy, University of Jember, Jember 68121, Indonesia.
2Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia.
Volume - 14,
Issue - 9,
Year - 2021
This study aimed to improve the solubility of quercetin by solvent pH control method and crystal modification through co-crystal formation using isonicotinamide as its co-former. Solubility of quercetin was tested at nine pH levels using phosphate buffer solvents. Quercetin-isonicotinamide co-crystal was prepared by a solvent evaporation method. Co-crystal preparation was carried out using two different stoichiometric ratios of quercetin-isonicotinamide (1:1 and 1:3). The co-crystalline solubility test was performed in 50 mL citrate buffer (pH 5.0 ± 0.05) at a temperature of 37 ± 0.5?C. The thermodynamic parameters of quercetin and co-crystal were analyzed to determine the mechanism of the quercetin solubility process. Increasing the pH of solvents has proven to increase the solubility of quercetin. The quercetin oxidation reaction starts at pH level of 7.4. The formation of quercetin-isonicotinamide co-crystal at ratio of 1:1 and 1:3 shows the increase of quercetin solubility by 1.36 and 1.27 times, respectively. The thermodynamic parameters of the quercetin and quercetinco-crystal, which include entropy, enthalpy, and free energy values, can be used to explain the solubility process of quercetin. Quercetin has increased solubility under alkaline pH conditions, but undergoes an oxidation reaction at pH 7.4 and easily oxidized at alkaline pH. Crystal modification of quercetin by the co-crystal formation method has proven to increase the solubility of quercetin so that it can be used for the development of quercetin as a candidate for effective, safe, and acceptable active pharmaceutical ingredient.
Cite this article:
Budipratiwi Wisudyaningsih, Solihatus Sallama, Siswandono, Dwi Setyawan. The Effect of pH and Cocrystal Quercetin-Isonicotinamide on Quercetin Solubility and its Thermodynamic. Research Journal of Pharmacy and Technology. 2021; 14(9):4657-1. doi: 10.52711/0974-360X.2021.00809
Budipratiwi Wisudyaningsih, Solihatus Sallama, Siswandono, Dwi Setyawan. The Effect of pH and Cocrystal Quercetin-Isonicotinamide on Quercetin Solubility and its Thermodynamic. Research Journal of Pharmacy and Technology. 2021; 14(9):4657-1. doi: 10.52711/0974-360X.2021.00809 Available on: https://rjptonline.org/AbstractView.aspx?PID=2021-14-9-23
1. Kashyap D, Sharma A, Tuli HS, Sak K, Garg VK, Buttar HS, Setzer WN, Sethi G. Apigenin: A natural bioactive ﬂavone-type molecule with promising therapeutic function. J. Funct. Foods. 2018; 48: 457–471.
2. Parameswari P, Devika R. In silico Molecular Docking Studies of Quercetin Compound against Anti-inflammatory and Anticancer Proteins. Research J. Pharm. and Tech. 2019; 12(11): 5305-5309.
3. Atashpour S, Fouladdel S, Movahhed TK, Barzegar E, Hossein M, Ostad SN, Azizi E. Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin. J. Basic Med. Sci. 2015; 18: 635–643.
4. WangW, Sun C, Mao L, Ma P, Liu F, Yang J, Gao, Y. The biological activities, chemical stability, metabolism and delivery system of quercetin. Trends in Food Science & Technology. 2016; 56: 21-38.
5. Almeida AF, Borge GIA, Piskula M, Tudose A, Tudoreanu L, Valentova K, Williamson G, Santos CN. Bioavailability of Quercetin in Humans with a Focus on Interindividual Variation. Compr. Rev. Food Sci. Food Saf. 2018; 17: 714–73.
6. Anand DAV, Arulmoli R, Parasuraman S. Over views of Biological Importance of Quercetin: A Bioactive Flavonoid. Pharmacogn. Rev. 2016; 10: 84–89.
7. Xu D, Hu MJ, Wang YQ, Cui YL. Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application. Molecules.2019; 24: 11 – 28.
8. Setyawan D, Oktavia IP, Farizka R, Sari R. Physicochemical Characterization and In Vitro Dissolution Test of Quercetin-Succinic Acid Co-Crystals Prepared using Solvent Evaporation. Turk. J. Pharm. Sci.2017; 14(3): 280 – 284.
9. Wisudyaningsih B, Setyawan D,and Siswandono. Co-crystallization of Quercetin and Isonicotinamide using Solvent Evaporation Method. Tropical Journal of Pharmaceutical Research. 2019; 18(4): 697-702.
10. Chebotarev, AN, and Snigur DV. Study of Acid-Base Properties of Quercetin in Aqueous Solution by Color Measurements. Journal of Analytical Chemistry.2015; 70(1): 55 – 59.
11. Sinha USA, Maguire AR, Lawrence SE. Cocrystallization of Nutraceuticals. Cryst. Growth and Design. 2015; 15(2): 984 – 1009.
12. Gadade DD, and Pekamwar SS. Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development. Adv Pharm Bull.2016; 6(4): 479-494.
13. Lahamage SR, Darekar AB, Saudagar RB. Pharmaceutical Co-Crystallization. Asian J. Res. Pharm. Sci. 2016; 6(1): 51-58.
14. Thomas JE, Hayak UY, Jagadish PC, Koteshwara KB. Design and Characterization of Valsartan Co-Crystal to Improve Its Aqueous Solubility and Dissolution Behavior. Research J. Pharm. and Tech. 2017; 10(1): 26-30.
15. Samineni R, Chimakurthy J, Sumalatha K, Dharani G, Rachana J, Manasa K, Anitha P. Co-Crystals: A Review of Recent Trends in Co Crystallization of BCS Class II Drugs. Research J. Pharm. and Tech. 2019; 12(7): 3117-3124.
16. SamipillaiM, and Rohani S. The Role of Higher Coformer Stoichiometry Ratio in Pharmaceutical Cocrystals for Improving Their Solid-State Properties: The Cocrystal of Progesteron and 4-hydroxybenzoic acid. J. of Cryst. Growth.2018; 507: 32-45.
17. Jayasankar A, Reddy LS, Bethune SJ, Rodríguez-HornedoN. Role of Cocrystal and Solution Chemistry on the Formation and Stability of Cocrystals with Different Stoichiometry. Cryst. Growth & Design.2009; 9: 889-897.
18. Hashemzadeh N, Vahdati S, Mahmoodzadeh E, and Jouyban A. Thermodynamic Studies of Ketoconazole Solubility in Water + Ethanol Mixtures at Different Temperatures. Research in Pharmaceutical Sciences.2012; 7(5): 76-84.