Investigation of β-cyclodextrin–norfloxacin inclusion complexes. Part 1. Preparation, physicochemical and microbiological characterization

Abstract

Introduction: Drugs classified as class IV by the Biopharmaceutical Classification System present significant problems in relation to effective oral administration. In the case of antibiotics, the subsequently high doses required can enhance the emergence of microorganism resistance and lead to a low rate of patient treatment adherence. Objective: In an attempt to improve physicochemical properties and microbiological activity of norfloxacin, the aim of this study was to investigate different methods (coevaporation, kneading followed by freeze-drying or spray-drying) to obtain complexes of norfloxacin and different cyclodextrins. Methods: Guest–host interactions were investigated through a complete physical–chemical characterization and the dissolution profile and microbiological activity were determined. Results: The formation of a complex of norfloxacin and β-cyclodextrin (1:1), obtained by kneading followed by freeze drying, led to increased drug solubility, which could maximize the oral drug absorption. Conclusion: Moreover, the microbiological activity was enhanced by around 23.3%, demonstrating that the complex formed could represent an efficient drug delivery system.

Keywords:

• inclusion complex
• microbiological activity
• norfloxacin
• solubility
• β-cyclodextrin

Financial & competing interests disclosure

This study was supported by the National Counsel of Technological and Scientific Development (CNPq) and Coordination for Enhancement of Higher Education Personnel (CAPES). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The pKa was determined experimentally to verify the ionization of norfloxacin.

• Of the three cyclodextrins tested, β-cyclodextrin revealed the best interaction with norfloxacin in phase solubility studies.

• β-cyclodextrin and pH 3 were selected to produce the solid complexes.

• Physical–chemical characterization verified the formation of the inclusion complex.

• High amounts of norfloxacin could be encapsulated in β-cyclodextrin.

• Improvement in the dissolution could be obtained applying three different technologies.

• Kneading followed by freeze-drying led to the best complex characteristics.

• Higher microbiological activity and a better dissolution profile were achieved.

Notes