Crystal Engineering of Ibuprofen and Caffeine by Cocrystal Formation Using Solvent Evaporation and Slurry Methods
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Abstract
Ibuprofen is a pharmaceutical active compound used to treat mild to moderate pain and fever. However, ibuprofen has low solubility in water. One method to increase solubility is cocrystal formation. The ibuprofen cocrystal was prepared in this study using caffeine as a coformer at a 1:1 molar ratio via solvent evaporation and slurry methods. The results of the XRD and thermal analysis of the sample indicate that a new solid phase is formed in the specific sa mple, which is different from both of its constituent components. Morphologically, the resulting cocrystals show a change in shape from their constituent compounds as well as a change in size. The solubility test results show that cocrystal formation is able to increase the solubility of ibuprofen. The conclusion of this study is that ibuprofen cocrystals can be formed with the coformer caffeine at a molar ratio of 1:1 using the slurry method and solvent evaporation.
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References
[1] Wisudyaningsih B, Ameliana L. Effect of gelling agent and penetration enhancer on the release rate of ibuprofen-PEG 6000 solid dispersion from gel preparations. Pharm Educ. 2022;22(2):55–59. https://doi.org/10.46542/pe.2022.222.5559
[2] Yuliandra, Y., Zaini, E., Syofyan, S., Pratiwi, W., Putri, L.N., Pratiwi, Y.S., Arifin, H. Cocrystal of Ibuprofen–Nicotinamide: Solid-State Characterization and In Vivo Analgesic Activity Evaluation. Sci. Pharm. 2018;86 (23):2-11. https://doi.org/10.3390/scipharm86020023
[3] Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today. 2007;12(23–24):1068–75.
[4] Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins: basic science and product development. J Pharm Pharmacol. 2010;62(11):1607–21.
[5] Serajuddin AT. Salt formation to improve drug solubility. Adv Drug Deliv Rev. 2007;59(7):603–16.
[6] Thakuria R, Delori A, Jones W, Lipert MP, Roy L, Rodriguez-Hornedo N. Pharmaceutical Cocrystals and Poorly Soluble Drugs. Int J Pharm. 2013; 453(1):101-25. https://doi.org/10.1016/j.ijpharm.2012.10.043
[7] Pandey J, Prajapati P, Shimpi MR, Tandon P, Velaga SP, Srivastava A, et al. Studies of Molecular Structure, Hydrogen Bonding and Chemical Activity of a Nitrofurantoin-L-Proline Cocrystal: a Combined Spectroscopy and Quantum Chemical Approach. RSC Adv. 2016 ;6: 74135–54. https://doi.org/10.1039/C6RA13035F
[8] Bučar D-K, Henry RF, Lou X, Duerst RW, Borchardt TB, MacGillivray LR, et al. Cocrystals of caffeine and hydroxy-2-naphthoic acids: Unusual formation of the carboxylic acid dimer in the presence of a heterosynthon. Molecular pharmaceutics. 2007;4(3):339–46. https://doi.org/10.1021/mp070004b
[9] Barikah, K.Z., Yudi, W., Budipratiwi, W. Quercetin-Glycolic Acid Cocrystalization Using Solvent Evaporation and Slurry Methods. Indonesian Journal of Pharmaceutical Science and Technology. 2024; 11(3):305-312. https://doi.org/10.24198/ijpst.v11i3.43596
[10] Patil A, Biradar S, Khandagale N, Zambre V. Formulation and evaluation of fexofenadine hydrochloride–nutraceutical cocrystal to improve bioavailability through inhibition of P-glycoprotein mediated drug efflux. Int J Drug Deliv Technol. 2025;15(2):804-11
[11] Mugwiza E, Hahirwa I, Umumararungu T. A UV spectrophotometric method for simultaneous determination of ibuprofen and paracetamol concentration in suspensions. Rwanda Med J. 2023;80(3):49–56. doi:10.4314/rmj.v80i3.7
[12] Bashyal, S. Ibuprofen And Its Different Analytical And Manufacturing Methods: A Review. Asian Journal of Pharmaceutical and Clinical Research. 2018; 11(7):25-29. https://doi.org/10.22159/AJPCR.2018.V11I7.24484
[13] The United States Pharmacopeia, USP 30 The National Formulary, NF 25. Rockville: United States Pharmacopeial Convention, Inc.; 2007.
[14] Schultheiss, N., Newman, A. Pharmaceutical Cocrystals and Their Physicochemical Properties. Crystal Growth and Design. 2009; Vol.9 (6):2950-67. https://doi.org/10.1021/cg900129f
[15] Qiao, N., Li, M., Schlindwein, W., Malek, N.,Davies, A., Trappitt, G. Pharmaceutical Cocrystals: An Overview. International Journal of Pharmaceutics. 2011; Vol 419:1-11. https://doi.org/10.1016/j.ijpharm.2011.07.037
[16] Setyawan D, Sari R, Yusuf H, Primaharinastiti R. Preparation and characterization of artesunate–nicotinamide cocrystal by solvent evaporation and slurry method. Asian J Pharm Clin Res. 2014;7(1):62–5.
[17] Yuliandra Y, Zaini E, Syofyan S, Pratiwi W, Putri LN, Pratiwi YS, Arifin H. Cocrystal of ibuprofen–nicotinamide: solid-state characterization and in vivo analgesic activity evaluation. Sci Pharm. 2018;86(2):23. https://doi.org/10.3390/scipharm86020023
[18] United States Pharmacopeia (2018). Monographs, Caffeine. FCC. Rockville, MD: United States Pharmacopeia.
[19] Alatas, F., Sundani, S., Lucy, S., Ismunandar, Hidero, U. Cocrystal Formation Between Didanosine and Two Aromatic Acids. International Journal of Pharmacy and Pharmaceutical Sciences. 2013; 5(3):275-280.
[20] Sanphui, P. et al. Fast dissolving curcumin cocrystal. Crystal Growth and Design. 2011; 11(9):4135–4145. https://doi.org/10.1021/cg200704s
[21] Galichet, L., Moffat, A., Osselton, M., Widdop, B. Clarke's Analysis of Drugs and Poisons. London: Pharmaceutical Press; 2005.
[22] Friscic T, Jones W. Recent Advances in Understanding the Mechanism of Cocrystal Formation via Grinding. Cryst Growth Des. 2009;9(3):1621-37. https://doi.org/10.1021/cg800764n
[23] Child SL, Rodriguez Hornedo N, Sreenivas L, Jayasankar A, Maheshwari C, McCausland L, et al. Screening Strategies Based on Solubility and Solution Composition Generate Pharmaceutically Acceptable Cocrystals of Carbamazepine. Cryst Eng Comm. 2008;10(7): 856-864. https://doi.org/10.1039/B715396A