Improvement  in vitro  Dissolution Rate of Quercetin Using Cocrystallization of Quercetin-Malonic Acid

Dwi Setyawan; Sukma Adhi Permata; Ahmad Zainul; Maria Lucia Ardhani Dwi Lestari

doi:10.22146/ijc.28511

Improvement in vitro Dissolution Rate of Quercetin Using Cocrystallization of Quercetin-Malonic Acid

https://doi.org/10.22146/ijc.28511

Dwi Setyawan^(1*), Sukma Adhi Permata⁽²⁾, Ahmad Zainul⁽³⁾, Maria Lucia Ardhani Dwi Lestari⁽⁴⁾

(1) Department of Pharmaceutics, Faculty of Pharmacy, Universitas Airlangga, Jl. Dharmawangsa Dalam, Surabaya 60286, Indonesia
(2) Department of Pharmaceutics, Faculty of Pharmacy, Universitas Airlangga, Jl. Dharmawangsa Dalam, Surabaya 60286, Indonesia
(3) Department of Pharmaceutics, Faculty of Pharmacy, Universitas Airlangga, Jl. Dharmawangsa Dalam, Surabaya 60286, Indonesia
(4) Department of Pharmaceutics, Faculty of Pharmacy, Universitas Airlangga, Jl. Dharmawangsa Dalam, Surabaya 60286, Indonesia
(*) Corresponding Author

Abstract

The aim of the study was to improve the in-vitro dissolution rate of quercetin (Qu) using cocrystallization of quercetin. Cocrystals of quercetin (Co Qu) were produced with malonic acid (Ma) as coformer at ratio 1:2 using solvent evaporation method. Cocrystals quercetin-malonic acid (Co Qu-Ma) was characterized using Differential Thermal Analysis (DTA), Powder X-Ray Diffraction (PXRD), Scanning Electron Microscope (SEM), and Fourier Transforms Infrared Spectrophotometer (FTIR) and in-vitro dissolution study. A new endothermic peak at 277.9 °C was shown from the thermogram. Diffractogram of Co Qu-Ma showed a new diffraction peak at 2θ 9.81, 12.99, and 19.80°. Microphotograph showed that Qu and Ma exhibited a columnar-shaped and a pebble-shaped crystal, respectively, and FTIR wavenumber of O-H functional group of quercetin was shifted from its original position at 3411 to 3428 cm^-1 in the physical mixture (pm) of Qu-Ma and 3418 cm^-1 in Co Qu-Ma, respectively. The physicochemical characterizations using DTA, PXRD, SEM and FTIR indicated that Co Qu-Ma were successfully obtained through solvent evaporation method. The in-vitro dissolution rate of Co Qu-Ma was 95.30% at 60 min. Cocrystals effectively increased dissolution rate and dissolution efficiency in comparison to the pure quercetin and physical mixture of quercetin-malonic acid.

Keywords

quercetin; malonic acid; cocrystal; in vitro dissolution

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References

[1] Kaur, H., and Kaur, G., 2014, A critical appraisal of solubility enhancement techniques of polyphenols, J. Pharm., 2014, 180845.

[2] Setyawan, D., Oktavia, I.P., Farizka, R., and Sari, R., 2017, Physicochemical characterization and in vitro dissolution test of quercetin-succinic acid co-crystals prepared using solvent evaporation, Turk. J. Pharm. Sci., 14 (3), 280–284.

[3] Smith, A.J., Kavuru, P., Wojtas, L., Zaworotko, M.J., and Shytle, R.D., 2011, Cocrystals of quercetin with improved solubility and oral bioavailability, Mol. Pharmaceutics, 8 (5), 1867–1876.

[4] Setyawan, D., Fadhil, A.A., Juwita, D., Yusuf, H., and Sari, R., 2017, Enhancement of solubility and dissolution rate of quercetin with solid dispersion system formation using hydroxypropyl methyl cellulose matrix, Thai J. Pharm. Sci., 41 (3), 112–116.

[5] Dian, L., Yu, E., Chen, X., Wen, X., Zhang, Z., Qin, L., and Wu, C., 2014, Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles, Nanoscale Res. Lett., 9 (1), 684.

[6] Najar, A.A., and Azim, Y., 2014, Pharmaceutical co-crystals: A new paradigm of crystal engineering, J. Indian Inst. Sci., 94 (1), 45–68.

[7] Parmar, V.K., and Shah, S.A., 2013, Hydrochloride salt co-crystals: Preparation, characterization and physicochemical studies, Pharm. Dev. Technol., 18 (2), 443–453.

[8] Vasisht, K., Chadha, K., Karan, M., Bhalla, Y., Jena, A.K., and Chadha, R., 2016, Enhancing biopharmaceutical parameters of bioflavonoid quercetin by cocrystallization, CrystEngComm, 18, 1403–1415.

[9] Veverka, M., Dubaj, T., Galllovič, J., Jorík, V., Veverková, E., Danihelová, M., and Šimon P., 2015, Cocrystals of quercetin: Synthesis, characterization, and screening of biological activity, Monatsh. Chem., 146 (1), 99–109.

[10] Sekhon, B.S., 2012, Nutraceutical cocrystals: An overview, RGUHS J. Pharm. Sci., 2, 16–25.

[11] Setyawan, D., Sari, R., Yusuf, H., and Primaharinastiti, R., 2014, Preparation and characterization of artesunate-nicotinamide cocrystal by solvent evaporation and slurry method, Asian J. Pharm. Clin. Res., 7 (1), 62–65.

[12] Espinosa-Lara, J.C., Guzman-Villanueva, D., Arenas-García, J.I., Herrera-Ruiz, D., Rivera-Islas, J., Román-Bravo, P., Morales-Rojas, H., and Höpfl, H., 2012, Cocrystals of active pharmaceutical ingredients-Praziquantel in combination with oxalic, malonic, succinic, maleic, fumaric, glutaric, adipic, and pimelic acids, Cryst. Growth Des., 13 (1), 169–185.

[13] Xu, L.L., Chen, J.M., Yan, Y., and Lu, T.B., 2012, Improving the solubility of 6-mercaptopurine via cocrystals and salts, Cryst. Growth Des., 12 (12), 6004–6011.

[14] Wicaksono, Y., Setyawan, D., and Siswandono, S., 2017, Formation of ketoprofen-malonic acid cocrystal by solvent evaporation method, Indones. J. Chem., 17 (2), 161–166.

[15] Sarkar, A., and Rohani, S., 2015, Cocrystals of acyclovir with promising physicochemical properties, J. Pharm. Sci., 104 (1), 98–105.

[16] Kakran, M., Sahoo, N.G, Li, L., and Judeh, Z., 2012, Fabrication of quercetin nanoparticles by anti-solvent precipitation method for enhanced dissolution, Powder Technol., 223, 59–64.

[17] Thakuria, R., Delori, A., Jones, W., Lipert, M.P., Roy, L., and Rodríguez-Hornedo, N., 2013, Pharmaceutical cocrystals and poorly soluble drugs, Int. J. Pharm., 453 (1), 101–125.

[18] Surov, A.O., Voronin, A.P., Manin, A.N., Manin, N.G., Kuzmina, L.G., Churakov, A.V., and Perlovich, G.L., 2014, Pharmaceutical cocrystals of diflunisal and diclofenac with theophylline, Mol. Pharmaceutics, 11 (10), 3707–3715.

DOI: https://doi.org/10.22146/ijc.28511