Solubility Enhancement and Characterization of Tamoxifen Citrate Using Co-crystallization

https://doi.org/10.22146/ijc.70891

Dolih Gozali(1), Iyan Sopyan(2), Hairunnisa Hairunnisa(3), Siska Sari Marvita(4*)

(1) Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University, West Java 45363, Indonesia
(2) Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University, West Java 45363, Indonesia
(3) Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University, West Java 45363, Indonesia
(4) Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University, West Java 45363, Indonesia
(*) Corresponding Author

Abstract


Tamoxifen citrate (TC) is one of the anti-estrogen agents which has low solubility in the water. As TC is still used as the main therapy in breast cancer treatment, modifications are still being made to increase the solubility of TC for a successful treatment. In this research, co-crystallization of TC was performed using Nicotinamide (NIC), Isonicotinamide (ISO), Saccharin (SAC), Aspartame (ASP), and Benzoic Acid (BNZ) as a coformer with the molar ratio of 1:1, 1:2, and 2:1. Co-crystal was prepared by solvent drop grinding (SDG) and solvent evaporation (SE) methods using methanol. The results of the solubility test showed that TC-NIC and TC-ISO co-crystals with a 1:2 molar ratio made using the SDG and SE methods gave the best results. Meanwhile, the best dissolution test results were shown by TC-ISO co-crystals with a ratio of 1:2. Based on the characterization of physical stability, the SDG method resulted in more stable TC co-crystals than the SE method. Therefore, in this case, the SDG method could be more advantageous to be used for development in the field of co-crystallization.

Keywords


tamoxifen citrate; co-crystallization; solubility

Full Text:

Full Text PDF


References

American Cancer Society, 2018, Cancer Facts & Figures 2018, American Cancer Society, Atlanta, US.

Chowdhury, N., Vhora, I., Patel, K., Bagde, A., Kutlehria, S., and Singh, M., 2018, Development of hot melt extruded solid dispersion of tamoxifen citrate and resveratrol for synergistic effects on breast cancer cells, AAPS PharmSciTech, 19 (7), 3287–3297.

Nasr, M., Hashem, F., Abdelmoniem, R., Tantawy, N., and Teiama, M., 2020, In vitro cytotoxicity and cellular uptake of tamoxifen citrate-loaded polymeric micelles, AAPS PharmSciTech, 21 (8), 306.

SreeHarsha, N., Hiremath, J.G., Chilukuri, S., Aitha, R.K., Al-Dhubiab, B.E., Venugopala, K.N., Alzahrani, A.M., and Meravanige, G., 2019, An approach to enhance dissolution rate of tamoxifen citrate, Biomed Res. Int., 2019, 2161348.

Dengale, S.J., Ranjan, O.P., Hussen, S.S., Krishna, B.S.M., Musmade, P.B., Shenoy, G.G., and Bhat, K., 2014, Preparation and characterization of co-amorphous Ritonavir-Indomethacin systems by solvent evaporation technique: Improved dissolution behavior and physical stability without evidence of intermolecular interactions, Eur. J. Pharm. Sci., 62, 57–64.

Metilda, G.M., and Kumari, J.P., 2016, Physicochemical characterization of α-cyclodextrin complexes of tamoxifen citrate and phase solubility studies, Int. J. Pharm. Sci. Res., 7 (2), 681–688.

Mirzajani, F., Rafati, H., and Atyabi, F., 2010, Fabrication of biodegradable poly(d,l,-co-glycolide) nanoparticles containing tamoxifen citrate, Iran. Polym. J., 19 (6), 437–446.

Bestari, A.N., 2014, Penggunaan siklodekstrin dalam bidang farmasi, Majalah Farmaseutik, 10 (1), 197–201.

Abd Hashib, S., Anuar, N., Jamburi, N., Ahmad, N.F., and Abd Rahim, S., 2015, Screening for ibuprofen-sachharin co-crystal formation in wet milling, Appl. Mech. Mater., 754-755, 1002–1006.

Sathisaran, I., and Dalvi, S.V., 2018, Engineering co-crystals of poorly water-soluble drugs to enhance dissolution in aqueous medium, Pharmaceutics, 10 (3), 108.

Aakeröy, C.B., Fasulo, M.E., and Desper, J., 2007, Co-crystal or salt: Does it really matter?, Mol. Pharmaceutics, 4 (3), 317–322.

Zaini, E., Halim, A., Soewandhi, S.N., and Setyawan, D., 2011, Peningkatan laju pelarutan trimetoprim melalui metode ko-kristalisasi dengan nikotinamida, Jurnal Farmasi Indonesia, 5 (4), 205–212.

Kerr, H.E., Softley, L.K., Suresh, K., Nangia, A., Hodgkinson, P., and Evans, I.R., 2015, A furosemide-isonicotinamide co-crystal: An investigation of properties and extensive structural disorder, CrystEngComm, 17 (35), 6707–6715.

Budiman, A., Megantara, S., and Apriliani, A., 2019, Solid dosage form development of glibenclamide-aspartame co-crystal using the solvent evaporation method to increase the solubility of glibenclamide, Int. J. Appl. Pharm., 11 (3), 150–154.

Huang, Y., Zhou, L., Yang, W., Li, Y., Yang, Y., Zhang, Z., Wang, C., Zhang, X., and Yin, Q., 2019, Preparation of theophylline-benzoic acid co-crystal and on-line monitoring of co-crystallization process in solution by raman spectroscopy, Crystals, 9 (7), 329.

Zaworotko, M., 2008, Crystal engineering of co-crystals and their relevance to pharmaceuticals and solid-state chemistry, Acta Crystallogr., Sect. A: Found. Crystallogr., 64 (a1), C11–C12.

Gozali, D., Bahti, H.H., Soewandhi, S.N., and Abdassah, M., 2014, Pembentukan kokristal antara kalsium atorvastatin dengan isonikotinamid dan karakterisasinya, JUSAMI, 15 (2), 103–110.

Hiendrawan, S., Widjojokusumo, E., Veriansyah, B., and Tjandrawinata, R.R., 2017, Pharmaceutical salts of carvedilol: Polymorphism and physicochemical properties, AAPS PharmSciTech, 18 (4), 1417–1425.

Gamberini, M.C., Baraldi, C., Tinti, A., Palazzoli, F., and Ferioli, V., 2007, Vibrational study of tamoxifen citrate polymorphism, J. Mol. Struct., 840 (1-3), 29–37.

Qiao, N., Li, M., Schlindwein, W., Malek, N., Davies, A., and Trappitt, G., 2011, Pharmaceutical co-crystals: An overview, Int. J. Pharm., 419 (1-2), 1–11.

Fadhilah, Q., and Tjahjono, D.H., 2012, Hubungan kuantitatif struktur dan aktivitas senyawa turunan 3-haloasilaminobenzoilurea sebagai inhibitor pembentukan mikrotubulus, Acta Pharm. Indones., 37 (3), 76–82.

Alatas, F., Soewandhi, S.N., and Sasongko, L., 2014, Kelarutan dan stabilitas kimia kompleks didanosin dengan nikotinamid atau L-arginin, JUSAMI, 15 (2), 94–102.

Pagire, S.K., Korde, S.A., Whiteside, B.R., Kendrick, J., and Paradkar, A., 2013, Spherical crystallization of carbamazepine/saccharin co-crystals: Selective agglomeration and purification through surface interactions, Cryst. Growth Des., 13 (10), 4162–4167.

Sanphui, P., Babu, N.J., and Nangia, A., 2013, Temozolomide co-crystals with carboxamide coformers, Cryst. Growth Des., 13 (5), 2208–2219.

Fernandes, G.J., Rathnanand, M., and Kulkarni, V., 2019, Mechanochemical synthesis of carvedilol cocrystals utilizing hot melt extrusion technology, J. Pharm. Innovation, 14 (4), 373–381.

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

Bolla, G., Sanphui, P., and Nangia, A., 2013, Solubility advantage of tenoxicam phenolic co-crystals compared to salts, Cryst. Growth Des., 13 (5), 1988–2003.



DOI: https://doi.org/10.22146/ijc.70891

Article Metrics

Abstract views : 1663 | views : 688


Copyright (c) 2022 Indonesian Journal of Chemistry

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

 


Indonesian Journal of Chemistry (ISSN 1411-9420 / 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

Web
Analytics View The Statistics of Indones. J. Chem.