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Journal of Thermal Analysis and Calorimetry

, Volume 132, Issue 2, pp 1095–1103 | Cite as

Physico-chemical study of norfloxacin and metronidazole binary mixtures

  • Daniela-Crina Salceanu
  • Elena Pincu
  • Giovanna Bruni
  • Amedeo Marini
  • Viorica Meltzer
Article

Abstract

The physico-chemical characterization of norfloxacin commercial sample (NF), norfloxacin anhydrous form A (NFanhA), norfloxacin pentahydrate (NF·5H2O) and metronidazole (MZ) has been carried out. It was determined that the commercial sample is a mixture of 74% anhydrous NF form A and 26% hemipentahydrate NF. From XRPD analysis, it was observed that after the water loss, NF·5H2O undergoes a solid–solid transition and is converting to NFanhA. Solid–liquid equilibrium for NFanhA–MZ and NF·5H2O–MZ binary systems has been investigated using differential scanning calorimetry, and simple eutectic point was observed, in good approximation, at 419 K for all the mixtures studied. The experimental solid–liquid phase diagram was compared with predictions obtained from available eutectic equilibrium models. The results indicate non-ideality for the mixture. The mixing enthalpy was determined at the eutectic composition and the negative value obtained, ΔMH = − 13.28 kJ mol−1, indicates that molecules of the two components form clusters in the eutectic melt.

Keywords

Norfloxacin Metronidazole Phase equilibrium Eutectic Combined medicine 

Notes

Acknowledgements

This work was possible with the financial support of the Sectoral Operational Programme for Human Resources Development 2007–2013, co-financed by the European Social Fund, under the Project Number POSDRU/107/1.5/S/80765.

References

  1. 1.
    Guul SJ, Os I, Jounela AJ. The efficacy and tolerability of enalapril in a formulation with a very low dose of hydrochlorothiazide in hypertensive patients resistent to enalapril monotherapy. Am J Hypertens. 1995;8:727–31.CrossRefGoogle Scholar
  2. 2.
    Huang SM, Temple R, Throckmorton DD, Lesko LJ. Drug interaction studies: study design, data analysis, and implications for dosing and labeling. Clin Pharmacol Ther. 2007;81:298–304.CrossRefGoogle Scholar
  3. 3.
    Wertheimer AI, Morrison A. Combination drugs: innovation in pharmacotherapy. P&T. 2002;27:44–9.Google Scholar
  4. 4.
    Kedderis GL. Pharmacokinetics of drug interactions. Adv Pharmacol. 1997;43:189–203.CrossRefGoogle Scholar
  5. 5.
    Sultana N, Arayne MS, Naveed S. Simultaneous quantitation of captopril and NSAID’s in API, dosage formulations and human serum by RP-HPLC. J Chin Chem Soc. 2010;57:62–7.CrossRefGoogle Scholar
  6. 6.
    Chandra Avula SG, Alexander K, Riga A. Thermal analytical characterization of mixtures of antipsychotic drugs with various excipients for improved drug delivery. J Therm Anal Calorim. 2016;123(3):1981–92.CrossRefGoogle Scholar
  7. 7.
    Sekiguchi K, Obi N. Studies on absorption of eutectic mixture. I. A comparison of the behavior of eutectic mixture of sulfathiazole and that of ordinary sulfathiazole in man. Chem Pharm Bull. 1961;9:866–72.CrossRefGoogle Scholar
  8. 8.
    Avula SG, Alexander K, Riga A. Predicting eutectic behavior of drugs and excipients by unique calculations. J Therm Anal Calorim. 2010;99(2):655–8.CrossRefGoogle Scholar
  9. 9.
    Lerdkanchanaporn S, Dollimore D, Evans SJ. Phase diagram for the mixtures of ibuprofen and stearic acid. Thermochim Acta. 2001;367–368:1–8.CrossRefGoogle Scholar
  10. 10.
    Deveswaran R, Sravya M, Bharath S, Basavaraj BV, Madhavan V. Development of modified porous starch as a carrier to improve aqueous solubility. Adv Appl Sci Res. 2012;3:162–70.Google Scholar
  11. 11.
    Kiss D, Zelkó R, Novák C, Éhen Z. Application of DSC and NIRS to study the compatibility of metronidazole with different pharmaceutical excipients. J Therm Anal Calorim. 2006;84:447–51.CrossRefGoogle Scholar
  12. 12.
    Mazuel C. Norfloxacin. In: Florey K, editor. Analytical profiles of drug substances, vol. 20. San Diego: Academic Press; 1991. p. 557–600.CrossRefGoogle Scholar
  13. 13.
    Chongcharoen W, Byrn SR, Sutanthavibul N. Solid state interconversion between anhydrous norfloxacin and its hydrates. J Pharm Sci. 2008;97:473–89.CrossRefGoogle Scholar
  14. 14.
    Roy S, Goud NR, Babu Jagadeesh N, Iqbal J, Kruthiventi AK, Nangia A. Crystal structures of norfloxacin hydrates. Cryst Growth Des. 2008;8:4343–6.CrossRefGoogle Scholar
  15. 15.
    Katdare AV, Ryan JA, Bavitz JF, Erb DM, Guillory JK. Characterization of hydrates of norfloxacin. Mikrochim Acta. 1986;3:1–12.CrossRefGoogle Scholar
  16. 16.
    Florence AJ, Kennedy AR, Shankland N, Wright E, Al-Rubayi A. Norfloxacin dihydrate. Acta Crystallogr Sect. 2000;C56:1372–3.Google Scholar
  17. 17.
    Puechagut HG, Bianchotti J, Chiale CA. Preparation of norfloxacin spherical agglomerates using the ammonia diffusion system. J Pharm Sci. 1998;87:519–23.CrossRefGoogle Scholar
  18. 18.
    Yuasa R, Imai J, Morikawa H, Kusajima H, Uchida H, Irikura T. Pharmaceutical studies on hydrates of AM-715. Physical characteristics and intestinal absorption. Yakugaku Zasshi. 1982;102:469–76.CrossRefGoogle Scholar
  19. 19.
    Deepika M, Jain A, Maheshwari RK, Patidar V. Simultaneous spectrophotometric estimation of metronidazole and norfloxacin in combined tablet formulations using hydrotrophy. Asian J Pharmacol. 2008;1:357–61.Google Scholar
  20. 20.
    Bharadwaj R, Vidya A, Dewan B, Pal A. An in vitro study to evaluate the synergistic activity of norfloxacin and metronidazole. Indian J Pharmacol. 2003;35:220–6.Google Scholar
  21. 21.
    Puigjaner C, Barbas R, Portell A, Font-Bardia M, Alcobe X, Prohens R. Revisiting of the solid state of norfloxacin. Cryst Growth Des. 2010;10:2948–53.CrossRefGoogle Scholar
  22. 22.
    Barbas R, Prohens R, Puigjaner C. A new polymorph of Norfloxacin. Complete characterization and relative stability of its trimorphic system. J Therm Anal Calorim. 2007;89:687–92.CrossRefGoogle Scholar
  23. 23.
    Gomes A, Correia L, da Silva Simoes MO, Macedo RO. Development of thermogravimetric method for quantitative determination of metronidazole. J Therm Anal Calorim. 2007;88:383–7.CrossRefGoogle Scholar
  24. 24.
    Deveswaran R, Sravya M, Bharath S, Basavaraj BV, Madhavan V. Development of modified porous starch as a carrier to improve aqueous solubility. Adv Appl Sci Res. 2012;3:162–70.Google Scholar
  25. 25.
    Ramukutty S, Ramachandran E. Crystal growth by solvent evaporation and characterization of metronidazole. J Cryst Growth. 2012;351:47–50.CrossRefGoogle Scholar
  26. 26.
    Bhowmik BB, Nayak BS, Chatterjee A. Formulation development and characterization of metronidazole microencapsulated bioadhesive vaginal gel. Int J Pharm Pharm Sci. 2009;1:240–57.Google Scholar
  27. 27.
    Herman C, Haut B, Aerts L, Leyssens T. Solid-liquid phase diagrams for the determination of the solid state nature of both polymorphs of (RS)-2-(2-oxo-pyrrolidin-1-yl)-butyramide. Int J Pharm. 2012;437:156–61.CrossRefGoogle Scholar
  28. 28.
    Prankerd RJ, Elsabee MZ. Thermal analysis of chiral drug mixtures: the DSC behavior of mixtures of ephedrine HCl and pseudoephedrine HCl enantiomers. Thermochim Acta. 1995;248:147–60.CrossRefGoogle Scholar
  29. 29.
    Klímová K, Leitner J. DSC study and phase diagrams calculation of binary systems of paracetamol. Thermochim Acta. 2012;550:59–64.CrossRefGoogle Scholar
  30. 30.
    Costa MC, Boros LAD, Coutinho JAP, Krahenbuhl MA, Meirelles AJA. Low-temperature behavior of biodiesel: solid–liquid phase diagrams of binary mixtures composed of fatty acid methyl esters. Energy Fuels. 2011;25:3244–50.CrossRefGoogle Scholar
  31. 31.
    Leitner J, Jurik S. DSC study and thermodynamic modelling of the system paracetamol–o-acetylsalicylic acid. J Therm Anal Calorim. 2017.  https://doi.org/10.1007/s10973-017-6404-3.Google Scholar
  32. 32.
    Marini A, Berbenni V, Bruni G, Sinistri C, Maggioni A, Orlandi A, Villa M. Physico-chemical characterization of a novel tricyclic β-lactam antibiotic. J Pharm Sci. 2000;89:232–40.CrossRefGoogle Scholar
  33. 33.
    Rai US, Pandey P, Rai RN. Physical chemistry of binary organic eutectic and monotectic alloys; 1,2,4,5-tetrachlorobengene and resorcinol system. Mater Lett. 2002;53:83–90.CrossRefGoogle Scholar
  34. 34.
    Rai US, Rai RN. Physical chemistry of organic analog of metal-metal eutectic and monotectic alloys. J Cryst Growth. 1998;191:234–42.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2018

Authors and Affiliations

  • Daniela-Crina Salceanu
    • 1
  • Elena Pincu
    • 1
  • Giovanna Bruni
    • 2
  • Amedeo Marini
    • 2
  • Viorica Meltzer
    • 1
  1. 1.Department of Physical Chemistry, Faculty of ChemistryUniversity of BucharestBucharestRomania
  2. 2.Department of Chemistry, Section of Physical Chemistry, C.S.G.IUniversity of PaviaPaviaItaly

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