The pH-solubility profiles of levofloxacin hemihydrate and ciprofloxacin lactate
DOI:
https://doi.org/10.46542/pe.2024.243.105110Keywords:
Ciprofloxacin lactate, Levofloxacin hemihydrate, pH buffer solution, pH-solubility profile, SolubilityAbstract
Background: Levofloxacin and ciprofloxacin are popular fluoroquinolone antibiotics that offer diverse therapeutic potentials due to their broad-spectrum activity. Levofloxacin and ciprofloxacin, commonly used as active pharmaceutical ingredients (API) in parenteral form, are amphoteric compounds with pH-sensitive solubility. This characteristic may affect the safety and efficacy of levofloxacin and ciprofloxacin, especially in the parenteral dosage forms.
Objective: This study aims to assess the solubility of levofloxacin hemihydrate and ciprofloxacin lactate in buffer solutions with pH ranging from 3.0 to 8.0.
Method: The solubility test was conducted in a 0.02 M buffer pH solution featuring an ionic strength (µ) of 0.2. After weighing several API samples, ultrasonication was carried out for 15 minutes. The solution was agitated at 150 rpm and 30 ± 0.5°C until it reached equilibrium (four hours). The API concentration was observed using a UV-Vis spectrophotometer.
Result: The solubility ranges of levofloxacin hemihydrate and ciprofloxacin lactate were 44.39 to 70.66 mg/mL and 0.23 to 243.00 mg/mL, respectively, within the experimental pH range.
Conclusion: This study concluded that levofloxacin hemihydrate and ciprofloxacin lactate solubility were increased due to decreasing pH medium.
References
Aulton, M. E., & Taylor, K. M. G. 2018. Aulton’s Pharmaceutics The Design and Manufacture of Medicines. Fifth Edition. Edinburgh: Elsevier Ltd.
Blokhina, S. V., Shaparova, A. V., Ol’khovich, M. V., Volkova, T. V., & Perlovich, G. L. (2016). Solubility, lipophilicity and membrane permeability of some floroquinolone antimicrobials. European Journal of Pharmaceutical Sciences, 93, 29‒37. http://doi.org/10.1016/j.ejps.2016.07.016
Czyrski, A. (2022). The spectrophotometric determination of lipophilicity and dissociation constants of ciprofloxacin and levofloxacin. Spectrochimica acta, 265, 120343. https://doi.org/10.1016/j.saa.2021.120343
Ezelarab, H. A. A., Abbas, S. H., Hassan, H. A., & Abuo-Rahma, G. E. A. (2018). Recent updates of fluoroquinolones as antibacterial agents. Archiv der Pharmazie, 351(9), e1800141. https://doi.org/10.1002/ardp.201800141
Florence, A. T., & Attwood, D. (2016). Physicochemical principles of pharmacy in manufacture, formulation and clinical use. London: Pharmaceutical Press.
Hansmann, S., Miyaji, Y., & Dressman, J. (2018). An in silico approach to determine challenges in the bioavailability of ciprofloxacin, a poorly soluble weak base with borderline solubility and permeability characteristics. European journal of pharmaceutics and biopharmaceutics, 122, 186–196. https://doi.org/10.1016/j.ejpb.2017.10.019
Isadiartuti, D., Rosita, N., Hendradi, E., Putri, F. F. D. P., & Magdalena, F. (2021). Solubility and Partition Coefficient of Salicylamide in Various pH Buffer Solutions. Indonesian Journal of Chemistry, 21(5), 1263‒1270. https://doi.org/10.22146/ijc.66411
Isadiartuti, D., Rosita, N., Syahrani, A., Ariyani, T., & Pramasari, N. (2022). pH adjustment and inclusion complex formation with hydroxypropyl-β-cyclodextrin to increase p-methoxycinnamic acid solubility. Journal of Chemical Technology and Metallurgy, 57(4), 723‒729.
Jalil, M. E. R., Baschini, M., & Sapag, K. (2015). Influence of pH and antibiotic solubility on the removal of ciprofloxacin from aqueous media using montmorillonite. Applied Clay Science, 114, 69‒76. https://doi.org/10.1016/J.CLAY.2015.05.010
Jiang, W. T., Wang, C. J., & Li, Z., 2013. Intercalation of ciprofloxacin accompanied by dehydration in rectorite. Applied Clay Science 74, 74‒80. https://doi.org/10.1016/j.clay.2012.07.009.
Koeppe, M. O., Cristofoletti, R., Fernandes, E. F., Storpirtis, S., Junginger, H. E., Kopp, S., Midha, K. K., Shah, V. P., Stavchansky, S., Dressman, J. B., & Barends, D. M. (2011). Biowaiver monographs for immediate release solid oral dosage forms: levofloxacin. Journal of Pharmaceutical Sciences, 100(5), 1628–1636. https://doi.org/10.1002/jps.22413
Nagasenkar, M. S., & Dhawan, V. V. (2020). Parenteral preparations, Remington: The Science and Practice of Pharmacy, pp. 577–603.
Parwe, S. P., Chaudhari, P. N., Mohite, K. K., Selukar, B. S., Nande, S. S.,Garnaik. (2014). Synthesis of ciprofloxacin-conjugated poly (L-lactic acid) polymer for nanofiber fabrication and antibacterial evaluation. International Journal of Nanomedicine, 9, 1463‒1477. https://doi.org/10.2147/IJN.S54971
Pavia, D. L., Lampman, G. M., Kriz, G. S., & Vyvyan, J. R. (2015). Introduction to spectroscopy, in Optical Astronomical Spectroscopy, 5th ed. Stamford: Cengage Learning.
Roethlisberger, D., Mahler, H. C., Altenburger, U., & Pappenberger, A. (2017). If euhydric and isotonic do not work, what are acceptable pH and osmolality for parenteral drug dosage forms? Journal of Pharmaceutical Sciences, 106(2), 446–456. https://doi.org/10.1016/j.xphs.2016.09.034
Sarısaltık, D., & Teksin, Z. Ş. (2007). Bioavailability file: Levofloxacin. FABAD Journal of Pharmaceutical Sciences, 32(4), 197‒209.
Sinko, P. J., & Sigh, Y. (2017). Martin’s physical pharmacy and pharmaceutical sciences: Physical chemical and biopharmaceutical principles in the pharmaceutical science, 7th Ed. Philadelphia: Lippincott William & Wilkins.
Vidyavathi, M., & Srividya, G., (2018). A review on ciprofloxacin: Dosage form perspective. International Journal of Applied Pharmaceutics, 10(4), 6‒10.
Wisudyaningsih, B., Sulwaldi, & Nugroho, A. K. (2014). Pengaruh pH dan kekuatan ionik terhadap profil kelarutan ofloksasin. Jurnal Ilmu Kefarmasian Indonesia, 12(1), 25‒31.
Yeon, K., Kim, J. H., Choi, K. E., Kim, D. H., & Lee, K. H., (1996). Salts of a quinolone-carboxylic acid. U.S. Patent