Formulation and characterization studies of inclusion complexes of voriconazole for possible ocular application

Abstract

In our study, Voriconazole (VOR) was selected as an active agent to be used for the treatment of ocular fungal infections. To overcome low aqueous solubility of VOR, inclusion complexes with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), hydroxypropyl-cyclodextrin (HP-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) hydroxypropyl-γ-cyclodextrin (HP-γ-CD), methyl-β-cyclodextrin (M-β-CD) and sulfabutylether-β-cyclodextrin (SBE-β-CD) were formulated. Characterization studies revealed that inclusion complexes were formulated successfully with the lyophilization method. Aqueous solubility of VOR was enhanced up to 86 fold with the formation of the inclusion complexes. MTT analyses results revealed the safety of the complexes on 3T3 mouse fibroblast cell lines while Microbroth Dilution Method revealed the remarkable antifungal activities of the complexes. Analyses results revealed that inclusion complexes will overcome the poor ocular bioavailability of VOR resulting inefficient treatment of severe ocular fungal infections.

Keywords:

• Voriconazole
• inclusion complexes
• lyophilization
• antifungal activity

Acknowledgement

The authors would like to thank Medicinal Plants, Drugs and Scientific Research Centre (AUBIBAM) management for SEM, Doping and Narcotic Substances Analysis Laboratory (DOPNA-LAB) for FT-IR and ¹H-NMR analyses to Eskişehir Technical University Faculty of Engineering and Architecture Department of Materials Engineering for XRD analyses.

Disclosure statement

The authors declare no conflict of interest about the study.

Additional information

Funding

The study was financed by The Scientific And Technological Research Council of Turkey (TÜBİTAK) with the Project Number of 216S731.