The crystallization of norfloxacin, an antibacterial fluoroquinolone compound, with different saturated aliphatic dicarboxylic acids yields five novel pharmaceutical salts via molecular recognition. In particular, a new norfloxacin-glutaric acid salt was obtained, which was characterized by infrared spectroscopy and powder X-ray diffraction. The effect of pKa on the solubility and dissolution profile of drug salts are investigated in pure water. After the formation of salts, the solubility increases at near neutral pH in all cases. Glutaric acid shows evidence of a good candidate to enhance the solubility of fluoroquinolone drugs for the solubility of 1 is approximately 27.7 times as large as that of norfloxacin in pure water.
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Zhu, L. , Huang, D. and Jiang, C. (2020). Study on the Influence of Saturated Aliphatic Dicarboxylic Acids on the Solubility of Their Norfloxacin Salts. Open Access Library Journal, 7, e6650. doi: http://dx.doi.org/10.4236/oalib.1106650.
Paulekuhn, G.S, Dressman, J.B. and Saal, C. (2007) Trends in Active Pharmaceutical Ingredient Salt Selection Based on Analysis of the Orange Book Database. Journal of Medicinal Chemistry, 50, 6665-6672. https://doi.org/10.1021/jm701032y
Bastin, R.J., Bowker, M.J. and Slater, B.J. (2000) Salt Selection and Optimisation Procedures for Pharmaceutical New Chemical Entities. Organic Process Research & Development, 4, 427-435. https://doi.org/10.1021/op000018u
Sanphui, P., Tothadi, S., Ganguly, S. and Desiraju, G.R. (2013) Salt and Cocrystals of Sildenafil with Dicarboxylic Acids: Solubility and Pharmacokinetic Advantage of the Glutarate Salt. Molecular Pharmaceutics, 10, 4687-4697.
https://doi.org/10.1021/mp400516b
Breda, S.A., Jimenez-Kairuz, A.F., Manzo, R.H. and Olivera, M.E. (2009) Solubility Behavior and Biopharmaceutical Classification of Novel High-Solubility Ciprofloxacin and Norfloxacin Pharmaceutical Derivatives. International Journal of Pharmaceutics, 371, 106-113. https://doi.org/10.1016/j.ijpharm.2008.12.026
Surov, A.O., Voronin, A.P., Drozd, K.V., Churakov, A.V., Roussel, P. and Perlovich, G.L. (2018) Diversity of Crystal Structures and Physicochemical Properties of Ciprofloxacin and Norfloxacin Salts with Fumaric Acid. CrystEngComm, 20, 755-767.
https://doi.org/10.1039/C7CE02033C
Basavoju, S., Boström, D. and Velaga, S.P. (2012) Pharmaceutical Salts of Fluoroquinolone Antibacterial Drugs with Acesulfame Sweetener. Molecular Crystals and Liquid Crystals, 562, 254-264. https://doi.org/10.1080/10426507.2012.669673
Bhattacharya, B., Mondal, A., Soni, S.R., Das, S., Bhunia, S., Bal Raju, K., et al. (2018) Multidrug Salt Forms of Norfloxacin with Non-Steroidal Anti-Inflammatory Drugs: Solubility and Membrane Permeability Studies. CrystEngComm, 20, 6420-6429.
https://doi.org/10.1039/C8CE00900G
Romañuk, C.B., Manzo, R.H., Linck, Y.G., Chattah, A.K., Monti, G.A. and Olivera, M.E. (2009) Characterization of the Solubility and Solid-State Properties of Saccharin Salts of Fluoroquinolones. Journal of Pharmaceutical Sciences, 98, 3788-3801.
https://doi.org/10.1002/jps.21688
Gopi, S.P., Ganguly, S. and Desiraju, G.R. (2016) A Drug-Drug Salt Hydrate of Nor？oxacin and Sulfathiazole: Enhancement of in Vitro Biological Properties via Improved Physicochemical Properties. Molecular Pharmaceutics, 13, 3590-3594.
https://doi.org/10.1021/acs.molpharmaceut.6b00320
Reddy, J.S., Ganesh, S.V., Nagalapalli, R., Dandela, R., Solomon, K.A., Kumar, K.A. and Nangia, A. (2011) Fluoroquinolone Salts with Carboxylic Acids. Journal of Pharmaceutical Sciences, 100, 3160-3176. https://doi.org/10.1002/jps.22537
