title: Investigation of β-cyclodextrin-norfloxacin inclusion complexes. Part 2. Inclusion mode and stability studies.
abstract: BACKGROUND
  Norfloxacin (NFX) is a broad spectrum antibiotic with low solubility and permeability, which is unstable on exposure to light and humidity.
  
  
  OBJECTIVE
  In this study, the mode of NFX inclusion into β-cyclodextrin complexes was evaluated and a complete physical, chemical and microbiological stability study of the inclusion complexes was carried out.
  
  
  METHODS
  Potentiometric titrations were performed to evaluate changes in the pKa of the NFX molecule due to the formation of an inclusion complex and NMR analysis demonstrated that the NFX molecule is included in the β-cyclodextrin cavity.
  
  
  RESULTS
  Inclusion complexes obtained by kneading followed by freeze-drying showed improved NFX stability compared with the isolated drug or the physical mixture. This method was effective in terms of protecting the drug from photodegradation and also avoiding hydrolysis. Differences between NFX and the complexes could be evidenced by thermal analysis, infrared spectroscopy and x-ray powder diffraction as well as by determining the solubility and drug content. The antimicrobial potency was also preserved on applying the promising method of kneading.
  
  
  CONCLUSIONS
  The satisfactory stability indicates that the NFX/β-cyclodextrin complexes could be useful as an alternative to the existing NFX drug formulation.
authors.affiliation: Post graduation Program in Pharmaceutical Sciences, Quality Control Laboratory, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil.
authors.forename: Cassiana
authors.initials: C
authors.lastname: Mendes
authors.forename: Aline
authors.initials: A
authors.lastname: Buttchevitz
authors.forename: Andersson
authors.initials: A
authors.lastname: Barison
authors.forename: Fernanda Maria Marins
authors.initials: FM
authors.lastname: Ocampos
authors.forename: Larissa Sakis
authors.initials: LS
authors.lastname: Bernardi
authors.forename: Paulo Renato
authors.initials: PR
authors.lastname: Oliveira
authors.forename: Marcos Antônio Segatto
authors.initials: MA
authors.lastname: Silva
mesh_terms: D000900:Anti-Bacterial Agents / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004055:Differential Thermal Analysis / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D024881:Drug Resistance, Bacterial; D004355:Drug Stability; D008855:Microscopy, Electron, Scanning / Q000379:methods; D009643:Norfloxacin / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis; D011199:Potentiometry / Q000379:methods; D033362:Powder Diffraction; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013678:Technology, Pharmaceutical / Q000379:methods*; D047392:beta-Cyclodextrins / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004364:Pharmaceutical Preparations; D047392:beta-Cyclodextrins; D009643:Norfloxacin
keywords: inclusion complexes; inclusion mode; norfloxacin; stability studies; β-cyclodextrin