Eudragit RS100 nanosuspensions for the ophthalmic controlled delivery of ibuprofen.
Topical application of non-steroidal anti-inflammatory drugs on the eye is a common treatment used to contrast the miosis induced by surgical traumas, such as cataract extraction. With the aim of improving the availability of sodium ibuprofen (IBU) at the intraocular level, IBU-loaded polymeric nanoparticle suspensions were made from inert polymer resins (Eudragit RS100). The nanosuspensions were prepared by a modification of the quasi-emulsion solvent diffusion technique using variable formulation parameters (drug-to-polymer ratio, total drug and polymer amount, stirring speed). Nanosuspensions had mean sizes around 100 nm and a positive charge (zeta-potential of +40/+60 mV), this makes them suitable for ophthalmic applications. Stability tests (up to 24 months storage at 4 degrees C or at room temperature) or freeze-drying were carried out to optimize a suitable pharmaceutical preparation. In vitro dissolution tests indicated a controlled release profile of IBU from nanoparticles. In vivo efficacy was assessed on the rabbit eye after induction of an ocular trauma (paracentesis). An inhibition of the miotic response to the surgical trauma was achieved, comparable to a control aqueous eye-drop formulation, even though a lower concentration of free drug in the conjunctival sac was reached from the nanoparticle system. Drug levels in the aqueous humour were also higher after application of the nanosuspensions; moreover, IBU-loaded nanosuspensions did not show toxicity on ocular tissues.
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Catania, Città Universitaria, viale A. Doria, 6 - 95125, Catania, Italy. pignatel@unict.it
Rosario
R
Pignatello
Claudio
C
Bucolo
Piera
P
Ferrara
Adriana
A
Maltese
Antonina
A
Puleo
Giovanni
G
Puglisi
D000180:Acrylic Resins; D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001082:Aqueous Humor / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007052:Ibuprofen / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D015877:Miosis / Q000517:prevention & control; D036103:Nanotechnology; D009883:Ophthalmic Solutions; D010316:Particle Size; D011817:Rabbits; D012995:Solubility; D013535:Suspensions
D000180:Acrylic Resins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D009883:Ophthalmic Solutions; D013535:Suspensions; C050528:Eudragit RS; D007052:Ibuprofen