AAPS PharmSciTech

, Volume 16, Issue 3, pp 683–691 | Cite as

Influence of β-cyclodextrin on the Properties of Norfloxacin Form A

  • Lucas ChierentinEmail author
  • Claudia Garnero
  • Ana Karina Chattah
  • Poonam Delvadia
  • Thomas Karnes
  • Marcela Raquel Longhi
  • Hérida Regina Nunes Salgado
Research Article


Cyclodextrins are able to form host–guest complexes with hydrophobic molecules to result in the formation of inclusion complexes. The complex formation between norfloxacin form A and β-cyclodextrin was studied by exploring its structure affinity relationship in an aqueous solution and in the solid state. Kneading, freeze-drying, and physical mixture methods were employed to prepare solid complexes of norfloxacin and β-cyclodextrin. The solubility of norfloxacin significantly increased upon complexation with β-cyclodextrin as demonstrated by a solubility isotherm of the AL type along with the results of an intrinsic dissolution study. The complexes were also characterized in the solid stated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffractometry, scanning electron microscopy (SEM), and solid-state nuclear magnetic resonance (ssNMR) spectrometry. The thermal analysis showed that the thermal stability of the drug is enhanced in the presence of β-cyclodextrin. Finally, the microbiological studies showed that the complexes have better potency when compared with pure drug.


bioassay complexation intrinsic dissolution norfloxacin β-cyclodextrin 



The authors are grateful to PACD-FCFAr-UNESP (Araraquara-Brazil), FAPESP process no 2010/13335-2 (São Paulo-Brazil) and CNPQ (Brasília-Brazil) for the fellowships and União Química (Minas Gerais-Brazil) for the financial support. In addition, the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), the Secretaría de Ciencia y Técnica de la Universidad Nacional de Córdoba (SECyT-UNC), and Ministerio de Ciencia y Tecnología (MinCyT) de la Provincia de Córdoba are grateful for the financial support. We also thank Ferromet S.A. (agent of Roquette in Argentina) for their donation of β-cyclodextrin. The cooperation from colleagues at the School of Pharmacy, Virginia Commonwealth University (VCU) is also highly appreciated. We also are grateful to Professor Peter R. Byron from VCU for his help and guidance with the intrinsic dissolution study.

Conflicts of Interest

The authors have declared no conflict of interest.


  1. 1.
    Naumann P, Dopp C. Fluoroquinolones—antibacterial activity, pharmacokinetics and indications for a new group of chemotherapeutic drugs. Internist (Berl). 1989;30:20–31.Google Scholar
  2. 2.
    Sárkozy G. Quinolones: a class of antimicrobial agents. Vet Med. 2001;46:257–74.Google Scholar
  3. 3.
    Bomma R, Naidu RAS, Yamsani MR, Veerabrahma K. Development and evaluation of gastroretentive norfloxacin floating tablets. Acta Pharm. 2009;59:211–21. doi: 10.2478/v10007-009-0019-6.CrossRefPubMedGoogle Scholar
  4. 4.
    Deng B, Su C, Kang Y. Determination of norfloxacin in human urine by capillary electrophoresis with electrochemiluminescence detection. Anal Bional Chem. 2006;371(385):1336–41.CrossRefGoogle Scholar
  5. 5.
    United States Pharmacopeia. 35th ed. Rockville: United States Pharmacopoeial Convention, 2012.Google Scholar
  6. 6.
    Barbas R, Martí F, Prohens R, Puigjaner C. Polymorphism of norfloxacin: evidence of the enantiotropic relationship between polymorphs A and B. Cryst Growth Des. 2006;6:1463–67. doi: 10.1021/cg060101u.CrossRefGoogle Scholar
  7. 7.
    Barbas R, Prohens R, Puigjaner C. A new polymorph of norfloxacin. J Therm Anal Calorim. 2007;89:687–92.CrossRefGoogle Scholar
  8. 8.
    Puigjaner C, Barbas B, Portell A, Font-Bardia M, Alcobé X, Prohens R. Revisiting of the solid state of norfloxacin. Cryst Growth Des. 2010;10:2948–53. doi: 10.1021/cg9014898.CrossRefGoogle Scholar
  9. 9.
    Szejtli J. Past, present, and future of cyclodextrin. Pure Appl Chem. 2004;76:1825–45.CrossRefGoogle Scholar
  10. 10.
    Challa R, Ahuja A, Ali J, Khar RK. Cyclodextrins in drug delivery: an updated review. AAPS PharmSciTech. 2005;6:329–57. doi: 10.1208/pt060243.CrossRefGoogle Scholar
  11. 11.
    Szejtli J. Cyclodextrins properties and applications. Drug Invest. 1990;2:11–21.CrossRefGoogle Scholar
  12. 12.
    Marques HC. Applications of cyclodextrins. Rev Port Farm. 1994;44:85–96.Google Scholar
  13. 13.
    Ali N, Harikumar SL, Amanpreet K. Cyclodextrin: an excipient tool in drug delivery. Int Res J Pharm. 2012;3:44–50.Google Scholar
  14. 14.
    Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci. 1996;85:1017–25.CrossRefPubMedGoogle Scholar
  15. 15.
    Lee PS, Han JY, Song TW, Sung JH, Kwon OS, Song S, et al. Physicochemical characteristics and bioavailability of a novel intestinal metabolite of ginseng saponin (IH901) complexes with β-cyclodextrin. Int J Pharm. 2006;316:29–36.CrossRefPubMedGoogle Scholar
  16. 16.
    Shen YL, Ying W, Yang SH, Wu LM. Determination of inclusion complex between gossypol and β-cyclodextrin. Spectrochim Acta A. 2006;65:169–72.CrossRefGoogle Scholar
  17. 17.
    Loftsson T, Duchêne D. Cyclodextrins and their pharmaceutical applications. Int J Pharm. 2007;329:1–11.CrossRefPubMedGoogle Scholar
  18. 18.
    Swanson BN, Boppana VK, Vlasses PH, Rotmensch HH, Ferguson RK. Norfloxacin disposition after sequentially increasing oral doses. Antimicrob Agents Chemother. 1983;23:284–88.PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Ross DL, Riley CM. Aqueous solubilities of some variously substituted quinolone antimicrobials. Int J Pharm. 1990;63:237–50. doi: 10.1016/0378-5173(90)90130-V.CrossRefGoogle Scholar
  20. 20.
    Tripathi KD. Essentials of medical pharmacology. 40th ed. New Delhi: Jaypee Brothers Medical Publishers (P) Ltd; 1999.Google Scholar
  21. 21.
    Guyot M, Fawaz F, Bildet J, Bonini F, Lagueny AM. Physicochemical characterization and dissolution of norfloxacin/cyclodextrin inclusion compounds and PEG solid dispersions. Int J Pharm. 1995;123:53–63. doi: 10.1016/0378-5173(95)00039-L.CrossRefGoogle Scholar
  22. 22.
    Fawaz F, Bonini F, Guyot N, Bildet J, Maury M, Lagueny AM. Bioavailability of norfloxacin from PEG 6000 solid dispersion and cyclodextrin inclusion complex in rabbits. Int J Pharm. 1996;132:271–75. doi: 10.1016/0378-5173(95)04387-X.CrossRefGoogle Scholar
  23. 23.
    Dua K, Ramana MV, Sara UV, Himaja M, Agrawal A, Garg V, et al. Investigation of enhancement of solubility of norfloxacin β-cyclodextrin in presence of acidic solubilizing additives. Curr Drug Deliv. 2007;4:21–5.CrossRefPubMedGoogle Scholar
  24. 24.
    Chattah AK, Mroue KH, Pfund LY, Ramamoorthy A, Longhi MR, Garnero C. Insights into novel supramolecular complexes of two solid forms of norfloxacin and β-cyclodextrin. J Pharm Sci. 2013;102:3717–24. doi: 10.1002/jps.23683.CrossRefPubMedGoogle Scholar
  25. 25.
    Higuchi T, Connors KA. Phase-solubility techniques. Advances in analytical chemistry and instrumentation. New York: Wiley-Interscience; 1965. p. 117–212.Google Scholar
  26. 26.
    Harris RK. Nuclear magnetic resonance spectroscopy. London: Logman Scientific and Technical; 1994.Google Scholar
  27. 27.
    Khitrin AK, Fujiwara T, Akutsub H. Phase-modulated heteronuclear decoupling in NMR of solids. J Magn Reson. 2003;162:46–53. doi: 10.1016/S1090-7807(02)00173-8.CrossRefPubMedGoogle Scholar
  28. 28.
    Loftsson T, Hreinsdottir D, Masson M. Evaluation of cyclodextrin solubilization of drugs. Int J Pharm. 2005;302:18–28. doi: 10.1016/j.ijpharm.2005.05.042.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • Lucas Chierentin
    • 1
    Email author
  • Claudia Garnero
    • 2
  • Ana Karina Chattah
    • 3
  • Poonam Delvadia
    • 4
  • Thomas Karnes
    • 4
  • Marcela Raquel Longhi
    • 2
  • Hérida Regina Nunes Salgado
    • 1
  1. 1.Faculdade de Ciências FarmacêuticasUniversidade Estadual PaulistaAraraquaraBrazil
  2. 2.Departamento de Farmacia, Facultad de Ciencias Químicas and UNITEFA (CONICET)Universidad Nacional de Córdoba, Ciudad UniversitariaCórdobaArgentina
  3. 3.Facultad de Matemática, Astronomía y Física and IFEG (CONICET)Universidad Nacional de CórdobaCórdobaArgentina
  4. 4.Department of Pharmaceutics, School of PharmacyVirginia Commonwealth UniversityRichmondUSA

Personalised recommendations