Development of inclusion complex of brinzolamide with hydroxypropyl-β-cyclodextrin

Abstract

Glaucoma is an accumulative optic neuropathy resulted from increasing intraocular pressure. Brinzolamide (BRZ) is a kind of carbonic anhydrase inhibitors for glaucoma treatment. In this study, brinzolamide-hydroxypropyl-β-cyclodextrin (BRZ-HP-β-CD) inclusion complex was prepared by solvent evaporation method to improve the solubility of BRZ and enhance the therapeutic effect of BRZ. The formation of the inclusion complex was confirmed by Fourier transform infrared spectroscopy, differential scanning calorimeter and nuclear magnetic resonance spectroscopy. The solubility of BRZ increased about 10-fold after the formation of the BRZ-HP-β-CD inclusion complex. The in vitro corneal accumulative permeability of the inclusion complex increased 2.91-fold compared to the commercial available formulation (AZOPT(®)). In addition, BRZ-HP-β-CD inclusion complex (0.5% BRZ) had an equivalent efficiency of lowering intraocular pressure with AZOPT(®) (1% BRZ) in vivo. These results identified the BRZ-HP-β-CD inclusion complex might have a promising future as a novel formulation of BRZ for glaucoma treatment.

Keywords: Brinzolamide; Cornea permeability; Glaucoma; Hydroxypropyl-β-cyclodextrin; Inclusion complex; Intraocular pressure.