INTRODUCTION: 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. CONCLUSION: The satisfactory stability indicates that the NFX/β-cyclodextrin complexes could be useful as an alternative to the existing NFX drug formulation.
INTRODUCTION: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. CONCLUSION: The satisfactory stability indicates that the NFX/β-cyclodextrin complexes could be useful as an alternative to the existing NFX drug formulation.
Authors: Pollyanna P Maia; Sara Maria R de Sousa; Wagner B De Almeida; Luciana Guimarães; Clebio S Nascimento Journal: J Mol Model Date: 2016-08-24 Impact factor: 1.810