Formulation and evaluation of cubosomes drug delivery system for treatment of glaucoma: Ex-vivo permeation and in-vivo pharmacodynamic study

Abstract

Glaucoma, a chronic disease of elevated intraocular pressure, is considered as the first leading cause of blindness. Brimonidine tartrate (BRT), a hydrophilic drug with poor ocular bioavailability, is a glaucoma treatment that is used three times daily. The frequent administration of BRT hinders patient adherence to treatment. The aim of this work is to improve BRT ocular bioavailability and prolong its intraocular pressure lowering effect by the preparation of BRT loaded cubosomes. Cubosomal formulations were prepared according to a d-optimal design. The selected variables were the percent of the dispersed phase, the ratio of glyceryl monooleate to poloxamer 407, the type of surfactant and the surfactant concentration. The prepared formulations were characterized for their drug content, particle size, PDI, zeta potential and in-vitro release. The optimized formulation had a size of 157.2 ± 4.2 nm, PDI 0.22 ± 0.03, a zeta potential of −30.2 ± 0.6mv and showed a sustained release pattern over 24 h. Micrographs of the transmission electron microscope confirmed the cubic nanostructure of the optimized formulation. Ex-vivo corneal permeation showed 1.6 folds enhanced permeability compared to Alphagan®P. The in-vivo pharmacodynamic study showed a 4.6 folds increase in AUC0–24h and 9.1 folds increase in the mean residence time compared to the market product Alphagan®P.