Development of a topical polymeric mucoadhesive ocular delivery system for azithromycin.
OBJECTIVE
Azithromycin is an azalide class of antibiotic with pharmacodynamics that have made it a valuable agent in the treatment of soft tissue infections. In ophthalmology, oral administration of azithromycin has been proven effective for the treatment of trachoma. However, topical formulations of azithromycin to treat ocular surface infections have been challenging to develop because of the drug's hydrophobicity and instability in aqueous solutions at pH levels that are comfortable in the eye. The design of a polycarbophil polymer-based delivery system for a topical formulation of azithromycin was evaluated for its ability to provide drug stability, comfort, and increased retention of the formulation in the eye.


METHODS
Formulations of 0.5% and 1.0% azithromycin were created in polycarbophil, a lightly cross-linked polyacrylic acid polymer that was adjusted to a viscosity, pH, and osmolality that are suitable for dispensing in the eye.


RESULTS
The polycarbophil-based ophthalmic delivery system, DuraSite (InSite Vision, Alameda, CA), helps solubilize azithromycin and retard its degradation in aqueous solution. The formulation was stable at room temperature as well as 5 degrees C. Upon administration of a single drop of 1% azithromycin in DuraSite ophthalmic solution in rabbits' eyes, tear concentrations of azithromycin ranged from 87 to 288 microg/g and high concentrations were sustained for over a 24-h period.


CONCLUSIONS
Azithromycin can be developed as an eyedrop in an aqueous ocular delivery system for the treatment of ocular surface infections. The ocular delivery system, DuraSite solubilizes azithromycin at a high concentration in an aqueous solution and protects it from degradation during manufacture and storage. The development of azithromycin in this delivery system enhances the antibiotic's usefulness in ophthalmology for the topical treatment of ocular surface bacterial infections and lid margin diseases.
Bowman
Lyle M
LM
Development and Operations, InSite Vision, Alameda, California 94501, USA. lylebo@insite.com
Si
Erwin
E
Pang
Joseph
J
Archibald
Roy
R
Friedlaender
Mitchell
M
D000180:Acrylic Resins; D000268:Adhesiveness; D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017963:Azithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D004337:Drug Carriers; D004355:Drug Stability; D009883:Ophthalmic Solutions; D011817:Rabbits; D012995:Solubility
D000180:Acrylic Resins; D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D009883:Ophthalmic Solutions; D017963:Azithromycin; C030312:calcium polycarbophil