Fabrication and Evaluation of Ketorolac Loaded Cubosome for Ocular Drug Delivery

Ophthalmic formulations in terms of eye drops are more frequently used formulation for ocular disorders. But unfortunately this mode of drug instillation into the cul-de-sac of eye shows very poor ocular bioavailability (less than 5%). A large number of carrier systems have been investigated to overcome this problem. In the present study a novel nano-carrier system (Ketorolac loaded cubosomes) is developed and evaluated for the safe and enhance ocular bioavailability. Cubosomes were developed and optimized by utilizing glyceryl mono-oleate, poloxamer 407 and initial drug concentration. Finally developed formulation was evaluated for various In vitro characteristics i.e. particles size, size distribution, shape and morphology, in-vitro release profile, corneal permeation, corneal retention, and ocular tolerance study. The optimized drug loaded cubosomal formulation showed mean particle size, polydispersity index, and entrapment efficiency 127.3±12.23 nm, 0.205±0.011, and 53.27±5.23 %, respectively. Transmission electron microscopic analysis revealed a cubic shape of developed formulation. Further, developed formulation exhibited biphasic release profile. Significant high transcorneal permeation (2.07 folds) and corneal retention (2.24 folds) of ketorolac was observed with cubosomal formulation correspond to Ketorolac solution (p<0.01). Further safety profile of optimized formulation was evaluated by histopathology of corneal membrane. The developed novel ocular carrier system (cubosomes) might be a promising platform as a vehicle for effective ocular drug delivery.