Effectiveness of ophthalmic solution preservatives: a comparison of latanoprost with 0.02% benzalkonium chloride and travoprost with the sofZia preservative system

Gerard Ryan,Karl M Gelotte,Cherie Lovelace,Joel M Fain

doi:10.1186/1471-2415-11-8

Gerard Ryan, Karl M Gelotte + Show 2 more

Open Access

https://doi.org/10.1186/1471-2415-11-8

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Abstract

BackgroundAlthough in vitro and in vivo laboratory studies have suggested that benzalkonium chloride (BAK) in topical ophthalmic solutions may be detrimental to corneal epithelial cells, multiple short- and long-term clinical studies have provided evidence supporting the safety of BAK. Despite the conflicting evidence, BAK is the most commonly used preservative in ophthalmic products largely due to its proven antimicrobial efficacy. This study was designed to characterize the antimicrobial performance of two commonly used topical ocular hypotensive agents that employ different preservative systems: latanoprost 0.005% with 0.02% BAK and travoprost 0.004% with sofZia, a proprietary ionic buffer system.MethodsEach product was tested for antimicrobial effectiveness by European Pharmacopoeia A (EP-A) standards, the most stringent standards of the three major compendia, which specify two early sampling time points (6 and 24 hours) not required by the United States Pharmacopeia or Japanese Pharmacopoeia. Aliquots were inoculated with between 105 and 106 colony-forming units of the test organisms: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Aspergillus brasiliensis. Sampling and enumeration were conducted at protocol-defined time points through 28 days.ResultsBAK-containing latanoprost met EP-A criteria by immediately reducing all bacterial challenge organisms to the test sensitivity and fungal challenges within the first six hours while the preservative activity of travoprost with sofZia did not. Complete bacterial reduction by travoprost with sofZia was not shown until seven days into the test, and fungal reduction never exceeded the requisite 2 logs during the 28-day test. Travoprost with sofZia also did not meet EP-B criteria due to its limited effectiveness against Staphylococcus aureus. Both products satisfied United States and Japanese pharmacopoeial criteria.ConclusionsLatanoprost with 0.02% BAK exhibited more effective microbial protection than travoprost with sofZia using rates of microbial reduction, time to no recovery for all challenges and evaluation against EP-A criteria as measures. The rapid and complete reduction of all microbial challenges demonstrates that antimicrobial activity of latanoprost with 0.02% BAK exceeds that of travoprost with sofZia preservative system in these products and provides a more protective environment in the event of contamination and subsequent exposure to microorganisms during use.

Highlights

In vitro and in vivo laboratory studies have suggested that benzalkonium chloride (BAK) in topical ophthalmic solutions may be detrimental to corneal epithelial cells, multiple short- and long-term clinical studies have provided evidence supporting the safety of BAK
This contamination translated into a high concordance of the same organisms cultured from the conjunctiva [1,2], especially in patients with ocular surface disease (OSD) [1]; one-third of patients reported having touched their eyes during medication installation [1]
Latanoprost ophthalmic solution 0.005% with 0.02% BAK exceeded European Pharmacopoeia-A (EP-A) criteria with reductions of all bacterial challenge microorganisms (≥4.7 log at 0 hours) and all fungal challenge microorganisms (≥4.4 log at 6 hours) (Table 3)

Summary

Introduction

In vitro and in vivo laboratory studies have suggested that benzalkonium chloride (BAK) in topical ophthalmic solutions may be detrimental to corneal epithelial cells, multiple short- and long-term clinical studies have provided evidence supporting the safety of BAK. Even when preserved with benzalkonium chloride (BAK), microbial contamination has been found to be present in 28% to 29% of in-use containers [1,2], with a significantly greater frequency in those used for more than 8 weeks [2]. This contamination translated into a high concordance of the same organisms cultured from the conjunctiva [1,2], especially in patients with ocular surface disease (OSD) [1]; one-third of patients reported having touched their eyes during medication installation [1]. Fort Worth, Texas, USA), another available formulation of travoprost ophthalmic solution

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