Safety of repeated topical ocular administration of a polycarbophil-based formulation in several models of ocular surgery in rabbits.

PURPOSE: To evaluate the safety of the polycarbophil-based formulation Durasite in rabbits when administered chronically to intact eyes and acutely to eyes compromised by a corneal epithelial defect, penetrating corneal incision, or laser in situ keratomileusis (LASIK) flap. The rheological properties were evaluated to characterize the behavior of the formulation on the ocular surface.

SETTING

Bausch & Lomb, Rochester, New York, USA.

DESIGN

Experimental study.

METHODS

Intact eyes of albino rabbits received polycarbophil (0.6% or 1.3%) 3 times a day for 1 year. The compromised models using polycarbophil 0.9% were an epithelial defect, penetrating corneal incision, or LASIK flap. Eyes with the epithelial defects were dosed 10 times for 24 hours and then 2 times a day for 2 days, and the defect was monitored with fluorescein. The incision or LASIK eyes were dosed 4 times a day for 11 days starting the day before surgery, with 1 drop just before the surgical procedure. The eyes were examined microscopically. The rheological properties were evaluated using a controlled-stress rheometer with a synthetic tear fluid.

RESULTS

No adverse ocular or systemic effects were observed with polycarbophil after chronic administration. In the compromised models, there were no adverse effects of the polycarbophil. There was no evidence of an anterior chamber reaction or qualitative effects on the corneal endothelium. Rheologically, the polycarbophil-based formulation behaved as a sheer-thinning fluid under physical conditions similar to the ocular surface.

CONCLUSION

Results suggest that the polycarbophil-based formulation, like other shear-thinning formulations, is safe to use in topical ophthalmic pharmaceutical products indicated for chronic use and for treatment of conditions with compromise of the ocular surface.