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Safety comparison of additives in antiglaucoma prostaglandin (PG) analog ophthalmic formulations

Authors Fukuda M, Shibata S, Shibata N, Hagihara K, Yaguchi H, Osada H, Takahashi N, Kubo E, Sasaki H

Received 9 November 2012

Accepted for publication 14 January 2013

Published 12 March 2013 Volume 2013:7 Pages 515—520


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Masamichi Fukuda, Shinsuke Shibata, Naoko Shibata, Kenta Hagihara, Hiromoto Yaguchi, Hiromi Osada, Nobuo Takahashi, Eri Kubo, Hiroshi Sasaki

Department of Ophthalmology, Kanazawa Medical University, Uchinada, Japan

Purpose: To investigate the safety of five types of antiglaucoma prostaglandin analog ophthalmic formulations, and to clarify their differences in accordance with contained additives (preservatives and surface-active agents).
Methods: The following five types of ophthalmic solutions and three types of additives were investigated: latanoprost (Xalatan®; latanoprost), tafluprost (Tapros®; tafluprost), bimatoprost (Lumigan®; bimatoprost), travoprost (Travatan®; travoprost), travoprost (Travatan Z®; travoprost-Z), benzalkonium chloride (BAK), polyoxyethylene hardening castor oil 40 (HCO-40), and polysorbate 80 (P-80). These experimental solutions were exposed to the cultured cells of a rabbit-derived corneal cell line for a certain time, and the exposure time causing 50% cell damage (CD50), indicated by the ratio of viable cells to total cells was calculated (in vitro). In addition, corneal resistance (CR) was measured and CR ratio (post-treatment CR/pretreatment CR × 100) was calculated (in vivo).
Results: CD50 of each ophthalmic solution was the longest with tafluprost, followed by travoprost-Z, bimatoprost, travoprost, and latanoprost. CD50 of 0.005%, 0.01%, and 0.02% BAK was 14.5 minutes, 8.1 minutes, and 4.0 minutes, respectively. The number of viable cells decreased to 60%, 8 minutes after exposure with HCO-40, and 30 minutes after being exposed to P-80. The CR ratio was 81.0% with travoprost and 82.0% with latanoprost, indicating a significant posttreatment reduction of CR (P < 0.05). The CR ratio did not decrease after treatment with tafluprost, travoprost-Z, or bimatoprost. The CR ratio of 0.005%, 0.01%, and 0.02% BAK was 105.0%, 90.5%, and 68.7%, respectively, and that of HCO-40 and P-80 was 108.7% and 114.2%, respectively.
Conclusion: BAK, HCO-40, and P-80 were thought to be involved in corneal injuries caused by each ophthalmic solution. Corneal injuries due to surface action were observed when using HCO-40 and P-80. When HCO-40 was combined with BAK, it induced micellar BAK and reduced corneal injuries by BAK.

Keywords: corneal resistance measuring device, additives, prostaglandin analogs, surface-active agents, corneal epithelial injury

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