Advertisement

AAPS PharmSciTech

, 20:278 | Cite as

Preparation, Characterization, and Properties of Inclusion Complexes of Balofloxacin with Cyclodextrins

  • Xiuyun Ren
  • Hongyun Qian
  • Peixiao Tang
  • Yuling TangEmail author
  • Yuanyuan Liu
  • Hongyu Pu
  • Man Zhang
  • Ludan Zhao
  • Hui LiEmail author
Research Article
  • 36 Downloads

Abstract

The study mainly aimed to improve the aqueous solubility of Balofloxacin (BLFX) by preparing the inclusion complexes (ICs) of BLFX with cyclodextrins (CDs). In this study, ICs in solid state were obtained by using beta-CD (β-CD), 2-hydroxypropyl-β-CD (HP-β-CD), 2, 6-dimethyl-β-CD (DM-β-CD) through a freeze-drying technique. The formation of ICs was confirmed through Fourier-transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, nuclear magnetic resonance, and scanning electron microscopy. Results demonstrated that the water solubility and dissolution rates of three ICs were distinctly improved than that of parent BLFX. Bacteriostatic experiment manifested that the antibacterial effect of BLFX was not inhibited after encapsulation in CDs. The damage of BLFX to kidney and liver cells was reduced. Consequently, successful preparation of the ICs of BLFX with CDs provided possibility for devising new dosage form of BLFX, which held great promise for further applications in clinical fields.

KEY WORDS

balofloxacin cyclodextrin inclusion complex solubility cytotoxicity 

Notes

Acknowledgments

We appreciated Hui Wang and Yueming Zhai from the Analytical & Testing Center of Sichuan University for helping with SEM and NMR characterization, respectively.

Funding Information

This work was supported by Sichuan Science and Technology Program (Grant No. 2018JY0188) and the Fundamental Research Funds for the Central Universities (Grant No. 2018SCU12043).

Supplementary material

12249_2019_1425_MOESM1_ESM.pdf (299 kb)
ESM 1 Fig. S1 Molecular structure of β-CD, HP-β-CD, and DM-β-CD. Fig. S2 Standard curve of BLFX. Fig. S3 Phase solubility curves of BLFX with CDs. Fig. S4 Antibacterial activity result against E. coli (a) and S. aureus (b) of pure BLFX (1), BLFX/β-CD IC (2), BLFX/HP-β-CD IC (3), BLFX/DM-β-CD IC (4) (PDF 298 kb)

References

  1. 1.
    Ezelarab HAA, Abbas SH, Hassan HA, Abuo-Rahma GEA. Recent updates of fluoroquinolones as antibacterial agents. Arch Pharm. 2018;351(9):e1800141.  https://doi.org/10.1002/ardp.201800141.CrossRefGoogle Scholar
  2. 2.
    Rizvi I, Malhotra HS, Garg RK, Kumar N, Uniyal R, Pandey S. Fluoroquinolones in the management of tuberculous meningitis: systematic review and meta-analysis. J Infect. 2018;77(4):261–75.  https://doi.org/10.1016/j.jinf.2018.06.009.CrossRefPubMedGoogle Scholar
  3. 3.
    Alovero F. In vitro pharmacodynamic properties of a fluoroquinolone pharmaceutical derivative: hydrochloride of ciprofloxacin–aluminium complex. Int J Antimicrob Agents. 2003;21(5):446–51.  https://doi.org/10.1016/s0924-8579(03)00051-7.CrossRefPubMedGoogle Scholar
  4. 4.
    DLRaCM R. Aqueous solubilities of some variously substituted quinolone antimicrobials. Int J Pharm. 1990;63:237–50.CrossRefGoogle Scholar
  5. 5.
    Zhang ZH, Zhang Q, Zhang QQ, Chen C, He MY, Chen Q, et al. From a binary salt to salt co-crystals of antibacterial agent lomefloxacin with improved solubility and bioavailability. Acta Crystallogr Sect B: Struct Sci Cryst Eng Mater. 2015;71(Pt 4):437–46.  https://doi.org/10.1107/S2052520615011191.CrossRefGoogle Scholar
  6. 6.
    Cheng Y, Qu H, Ma M, Xu Z, Xu P, Fang Y, et al. Polyamidoamine (PAMAM) dendrimers as biocompatible carriers of quinolone antimicrobials: an in vitro study. Eur J Med Chem. 2007;42(7):1032–8.  https://doi.org/10.1016/j.ejmech.2006.12.035.CrossRefPubMedGoogle Scholar
  7. 7.
    Qi Y, Zhao F, Xie X, Xu X, Ma Z. Study on the cofluorescence effect of europium (III)–yttrium (III)—Balofloxacin–sodium dodecyl sulfate system and its analytical application. Spectrosc Lett. 2014;48(5):311–6.  https://doi.org/10.1080/00387010.2013.879316.CrossRefGoogle Scholar
  8. 8.
    Tatsuya Ito MM, Nishino T. Improved bactericidal activity of Q-35 against quinolone-resistant staphylococci. Antimicrob Agents Chemother. 1995;39:1522–5.CrossRefGoogle Scholar
  9. 9.
    Osamu Kozawa TU, Matsuno H, Niwa M, Nagashima S, Kanamaru M. Comparative study of pharmacokinetics of two new fluoroquinolones, Balofloxacin and Grepafloxacin, in elderly subjects. Antimicrob Agents Chemother. 1996;40:2824–8.CrossRefGoogle Scholar
  10. 10.
    Suzuki K, MH KI, Katoh S, Naide Y, Yanaoka M, Andoh S. Laboratory and clinical study of Balofloxacin (Q-35), a new fluoroquinolone, in urinary tract infection. Drugs. 1995;49:376–8.CrossRefGoogle Scholar
  11. 11.
    Shelley H, Babu RJ. Role of cyclodextrins in nanoparticle-based drug delivery systems. J Pharm Sci. 2018;107(7):1741–53.  https://doi.org/10.1016/j.xphs.2018.03.021.CrossRefPubMedGoogle Scholar
  12. 12.
    Tang P, Sun Q, Suo Z, Zhao L, Yang H, Xiong X, et al. Rapid and efficient removal of estrogenic pollutants from water by using beta- and gamma-cyclodextrin polymers. Chem Eng J. 2018;344:514–23.  https://doi.org/10.1016/j.cej.2018.03.127.CrossRefGoogle Scholar
  13. 13.
    Tang P, Sun Q, Zhao L, Tang Y, Liu Y, Pu H, et al. A simple and green method to construct cyclodextrin polymer for the effective and simultaneous estrogen pollutant and metal removal. Chem Eng J. 2019;366:598–607.  https://doi.org/10.1016/j.cej.2019.02.117.CrossRefGoogle Scholar
  14. 14.
    Yujing Guo SG, Zhai JRY, Dong S, Wang E. Cyclodextrin functionalized graphene nanosheets with high supramolecular recognition capability synthesis and host-guest inclusion for enhanced electrochemical performance. ACS Nano. 2010;4:4001–10.CrossRefGoogle Scholar
  15. 15.
    Lopedota A, Denora N, Laquintana V, Cutrignelli A, Lopalco A, Tricarico D, et al. Alginate-based hydrogel containing minoxidil/hydroxypropyl-beta-cyclodextrin inclusion complex for topical alopecia treatment. J Pharm Sci. 2018;107(4):1046–54.  https://doi.org/10.1016/j.xphs.2017.11.016.CrossRefPubMedGoogle Scholar
  16. 16.
    Le-Deygen IM, Skuredina AA, Uporov IV, Kudryashova EV. Thermodynamics and molecular insight in guest–host complexes of fluoroquinolones with β-cyclodextrin derivatives, as revealed by ATR-FTIR spectroscopy and molecular modeling experiments. Anal Bioanal Chem. 2017;409(27):6451–62.  https://doi.org/10.1007/s00216-017-0590-5.CrossRefPubMedGoogle Scholar
  17. 17.
    Shi Y, Peng J, Meng X, Huang T, Zhang J, He H. Turn-on fluorescent detection of captopril in urine samples based on hydrophilic hydroxypropyl beta-cyclodextrin polymer. Anal Bioanal Chem. 2018;410(28):7373–84.  https://doi.org/10.1007/s00216-018-1343-9.CrossRefPubMedGoogle Scholar
  18. 18.
    Kurkov SV, Loftsson T. Cyclodextrins. Int J Pharm. 2013;453(1):167–80.  https://doi.org/10.1016/j.ijpharm.2012.06.055.CrossRefPubMedGoogle Scholar
  19. 19.
    Charoenchaitrakool M, Dehghani F, Foster NR. Utilization of supercritical carbon dioxide for complex formation of ibuprofen and methyl-β-cyclodextrin. Int J Pharm. 2002;239:103–12.CrossRefGoogle Scholar
  20. 20.
    Inoue Y, Watanabe S, Suzuki R, Murata I, Kanamoto I. Evaluation of actarit/γ-cyclodextrin complex prepared by different methods. J Incl Phenom Macrocycl Chem. 2014;81(1–2):161–8.  https://doi.org/10.1007/s10847-014-0445-z.CrossRefGoogle Scholar
  21. 21.
    Higuchi T, Connors KA. Phase solubility techniques. Adv Anal Chem Instrum 1965;4117–212.Google Scholar
  22. 22.
    Garnero C, Chattah AK, Aloisio C, Fabietti L, Longhi M. Improving the stability and the pharmaceutical properties of Norfloxacin form C through binary complexes with beta-cyclodextrin. AAPS PharmSciTech. 2018;19(5):2255–63.  https://doi.org/10.1208/s12249-018-1033-0.CrossRefPubMedGoogle Scholar
  23. 23.
    Wang L, Li S, Tang P, Yan J, Xu K, Li H. Characterization and evaluation of synthetic riluzole with beta-cyclodextrin and 2,6-di-O-methyl-beta-cyclodextrin inclusion complexes. Carbohydr Polym. 2015;129:9–16.  https://doi.org/10.1016/j.carbpol.2015.04.046.CrossRefPubMedGoogle Scholar
  24. 24.
    He Z, Wei G, Li N, Niu M, Gong S, Wu G, et al. CCR2 and CCR5 promote diclofenac-induced hepatotoxicity in mice. Naunyn Schmiedeberg's Arch Pharmacol. 2018;392:287–97.  https://doi.org/10.1007/s00210-018-1576-3.CrossRefGoogle Scholar
  25. 25.
    Yang R, Zhao Q, Hu DD, Xiao XR, Li F. Optimization of extraction and analytical protocol for mass spectrometry-based metabolomics analysis of hepatotoxicity. Biomed Chromatogr. 2018;32(12):e4359.  https://doi.org/10.1002/bmc.4359.CrossRefPubMedGoogle Scholar
  26. 26.
    Bian Z, Tian Y, Zhang Z, Xu F, Li J, Cao X. High performance liquid chromatography-electrospray ionization mass spectrometric determination of balofloxacin in human plasma and its pharmacokinetics. J Chromatogr B, Analytical technologies in the biomedical and life sciences. 2007;850(1–2):68–73.  https://doi.org/10.1016/j.jchromb.2006.11.001.CrossRefGoogle Scholar
  27. 27.
    Wang D, Chen G, Ren L. Preparation and characterization of the sulfobutylether-beta-cyclodextrin inclusion complex of amiodarone hydrochloride with enhanced oral bioavailability in fasted state. AAPS PharmSciTech. 2017;18(5):1526–35.  https://doi.org/10.1208/s12249-016-0646-4.CrossRefPubMedGoogle Scholar
  28. 28.
    Misiuk W, Jozefowicz M. Study on a host–guest interaction of hydroxypropyl-β-cyclodextrin with ofloxacin. J Mol Liq. 2015;202:101–6.  https://doi.org/10.1016/j.molliq.2014.12.029.CrossRefGoogle Scholar
  29. 29.
    Dsugi NF, Elbashir AA. Supramolecular interaction of moxifloxacin and beta-cyclodextrin spectroscopic characterization and analytical application. Spectrochim Acta A Mol Biomol Spectrosc. 2015;137:804–9.  https://doi.org/10.1016/j.saa.2014.08.081.CrossRefPubMedGoogle Scholar
  30. 30.
    Barbosa JS, Nolasco MM, Ribeiro-Claro P, Almeida Paz FA, Braga SS. Preformulation studies of the gamma-cyclodextrin and Montelukast inclusion compound prepared by comilling. J Pharm Sci. 2018;108:1837–47.  https://doi.org/10.1016/j.xphs.2018.11.047.CrossRefPubMedGoogle Scholar
  31. 31.
    Dsugi NF, Elbashir AA, Suliman FE. Supramolecular interaction of gemifloxacin and hydroxyl propyl beta-cyclodextrin spectroscopic characterization, molecular modeling and analytical application. Spectrochim Acta A Mol Biomol Spectrosc. 2015;151:360–7.  https://doi.org/10.1016/j.saa.2015.06.031.CrossRefPubMedGoogle Scholar
  32. 32.
    Ferreira LEN, Antunes GBM, Muniz BV, Burga-Sanchez J, de Melo NFS, Groppo FC, et al. Effects of lidocaine and the inclusion complex with 2-hydroxypropyl-beta-cyclodextrin on cell viability and proliferation of oral squamous cell carcinoma. J Pharm Pharmacol. 2018;70(7):874–82.  https://doi.org/10.1111/jphp.12917.CrossRefPubMedGoogle Scholar
  33. 33.
    Alves-Silva I, Sá-Barreto LCL, Lima EM, Cunha-Filho MSS. Preformulation studies of itraconazole associated with benznidazole and pharmaceutical excipients. Thermochim Acta. 2014;575:29–33.  https://doi.org/10.1016/j.tca.2013.10.007.CrossRefGoogle Scholar
  34. 34.
    Banchero M, Ronchetti S, Manna L. Characterization of ketoprofen/methyl-β-cyclodextrin complexes prepared using supercritical carbon dioxide. J Chem. 2013;2013:1–8.  https://doi.org/10.1155/2013/583952.CrossRefGoogle Scholar
  35. 35.
    Szabó Z-I, Deme R, Mucsi Z, Rusu A, Mare AD, Fiser B, et al. Equilibrium, structural and antibacterial characterization of moxifloxacin-β-cyclodextrin complex. J Mol Struct. 2018;1166:228–36.  https://doi.org/10.1016/j.molstruc.2018.04.045.CrossRefGoogle Scholar
  36. 36.
    Mangolim CS, Moriwaki C, Nogueira AC, Sato F, Baesso ML, Neto AM, et al. Curcumin-beta-cyclodextrin inclusion complex: stability, solubility, characterisation by FT-IR, FT-Raman, X-ray diffraction and photoacoustic spectroscopy, and food application. Food Chem. 2014;153:361–70.  https://doi.org/10.1016/j.foodchem.2013.12.067.CrossRefPubMedGoogle Scholar
  37. 37.
    Abdul Rauf Khan PF, Stine KJ, D’Souza VT. Methods for selective modifications of Cyclodextrins. Chem Rev. 1998;98:1977–96.CrossRefGoogle Scholar
  38. 38.
    Saenger W. Cyclodextrin inclusion compounds in research and industry. Angew Chem Int Ed Engl. 1980;19:344–62.CrossRefGoogle Scholar
  39. 39.
    Schneider HJ, Hacket F, Rüdiger V, Ikeda H. NMR studies of Cyclodextrins and Cyclodextrin complexes. Chem Rev. 1998;98:1755–85.CrossRefGoogle Scholar
  40. 40.
    Tang P, Li S, Wang L, Yang H, Yan J, Li H. Inclusion complexes of chlorzoxazone with beta- and hydroxypropyl-beta-cyclodextrin: characterization, dissolution, and cytotoxicity. Carbohydr Polym. 2015;131:297–305.  https://doi.org/10.1016/j.carbpol.2015.05.055.CrossRefPubMedGoogle Scholar
  41. 41.
    Rao MRP, Chaudhari J, Trotta F, Caldera F. Investigation of Cyclodextrin-based nanosponges for solubility and bioavailability enhancement of rilpivirine. AAPS PharmSciTech. 2018;19(5):2358–69.  https://doi.org/10.1208/s12249-018-1064-6.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Xiuyun Ren
    • 1
  • Hongyun Qian
    • 1
  • Peixiao Tang
    • 1
  • Yuling Tang
    • 2
    Email author
  • Yuanyuan Liu
    • 1
  • Hongyu Pu
    • 1
  • Man Zhang
    • 1
  • Ludan Zhao
    • 1
  • Hui Li
    • 1
    Email author
  1. 1.School of Chemical EngineeringSichuan UniversityChengduPeople’s Republic of China
  2. 2.National Engineering Laboratory for Clean Technology of Leather ManufactureSichuan UniversityChengduPeople’s Republic of China

Personalised recommendations