COMPARISON OF THIMEROSAL EFFECTIVENESS IN THE FORMULATION OF EYE DROPS CONTAINING NEOMYCIN SULFATE AND CHLORAMPHENICOL
Keywords:Thimerosal, Eye drops, Neomycin sulfate, Chloramphenicol
AbstractObjective: This study was aimed to compare the preservative efficacy of thimerosal in eye drops formulation containing neomycin sulfate and chloramphenicol as the active agents.Methods: Determination of thimerosal concentration in combinations with chloramphenicol and neomycin sulfate was carried out using the agar diffusion method. Then the thimerosal ineffective and minimal concentration was formulated into eye drops, each with 0.5% neomycin sulfate and 0.5% chloramphenicol as the active ingredient. Evaluation of eye drops was carried out for 28 d, which included: visual observation, pH measurement, sterility, and effectiveness test.Results: Thimerosal at a minimum concentration of 0.001% remain to provide antibacterial activity against common eyes contaminants. Both eyes drops containing neomycin sulfate, and chloramphenicol resulted in clear solution, sterile, and stable in the pH and antibacterial potency,showed the efficacy of thimerosal's role in eye drops at the lowest concentration. But, the thimerosal stability as a preservative agent was affected by the pH values of the eye drops solution. Therefore, the effectivity of thimerosal in chloramphenicol (pH 7.19-7.22) was better than neomycin sulfate (6.45-6.60). Compared with F0 (without thimerosal), the increasing of inhibitory diameter in F1 and F2 from both eyes drops formula exhibited the significant role of thimerosal as the preservative agent. The synergistic effect of the preservative agent in the formula produced a better product stability than the eye drop without thimerosal. Conclusion: Thimerosal at a minimum concentration of 0.001% exhibited effective concentration as a preservative in eye drops containing 0.5% neomycin sulfate and 0.5% chloramphenicol.
Menzies D, Bourbeau J. Building-related illnesses. N Engl J Med 1997;337:1524-31.
Stone V. Environmental air pollution. Am J Respir Crit Care Med 2000;162:S44-7.
Nunes ZG, Martins AS, Altoe AL. Indoor air microbiological evaluation of offices, hospitals, industries, and shopping centres. Mem Inst Oswaldo Cruz 2005;100:351-7.
Kusuma SAF, Hendriani R, Genta A. Antimicrobial spectrum of red piper betel leaf extract (Piper crocatum Ruiz and Pav) as natural antiseptics against airborne pathogens. J Pharm Sci Res 2017;9:583-7.
Mayo MS, Schlitzer RL, Ward MA, Wilson LA, Ahearn DG. Association of pseudomonas and serratia corneal ulcers with use of contaminated solutions. J Clin Microbiol 1987;25:1398â€“400.
Donzis PB. Corneal ulcer associated with contamination of aerosol saline spray tip. Am J Ophthalmol 1997;124:394â€“5.
Snyder RW, Glasser DB. Antibiotic therapy for ocular infection. West J Med 1994;161:579â€“84.
Templeton WC. 3rd Eiferman RA, Snyder JW, Melo JC, Raff MJ. Serratia keratitis transmitted by contaminated eyedroppers. Am J Ophthalmol 1982;93:723â€“6.
Schein OD, Wasson PJ, Boruchoff SA, Kenyon KR. Microbial keratitis associated with contaminated ocular medications. Am J Ophthalmol 1988;105:361â€“5.
Perry HD, Donnenfeld ED. Issues in the use of preservative-free topicals. Manag Care 2003;12:39â€“41.
Jokl DH, Wormser GP, Nichols NS, Montecalvo MA, Karmen CL. Bacterial contamination of ophthalmic solutions used in an extended care facility. Br J Ophthalmol 2007;91:1308â€“10.
Fazeli MR, Nejad HB, Mehrgan H. Microbial contamination of preserved ophthalmic drops in outpatient departments: possibility of an extended period of use. Daru 2004;12:151â€“6.
Geyer O, Bottone EJ, Podos SM, Schumer RA, Asbell PA. Microbial contamination of medications used to treat glaucoma. Br J Ophthalmol 1995;79:376â€“9.
Stevens JD, Matheson MM. Survey of the contamination of eyedrops of hospital inpatients and recommendations for the changing of current practice in eyedrop dispensing. Br J Ophthalmol 1992;76:36â€“8.
Brudieu E, Duc DL, Masella JJ, Croize J, Valence B, Meylan I, et al. Bacterial contamination of multi-dose ocular solutions. A prospective study at the Grenoble Teaching Hospital. Pathol Biol (Paris) 1999;47:1065â€“70.
Tasli H, Cosar G. Microbial contamination of eye drops. Cent Eur J Public Health 2001;9:162â€“4.
Feghhi M, Mahmoudabadis AZ, Mehdinejad M. Evaluation of fungal and bacterial contaminations of patient-used ocular drops. Med Mycol 2008;46:17-21.
Hooker B, Kern J, Geier D, Haley B, Sykes L, King P, et al. Methodological issues and evidence of malfeasance in research purporting to show thimerosal in vaccines is safe. BioMed Res Int 2014;1-8. http://dx.doi.org/10.1155/2014/247218
Maggs DJ, Miller P, Ofri R. Ocular pharmacology and therapeutics. Slatter's Fundamentals of Veterinary Ophthalmology. 4th ed. Saunders, California; 2008.
Buckley SA. Survey of patients taking topical medication at their first presentation to eye casualty. Br Med J 1990;300:1497-8.
Kirkness CM, Seal DV, Hay J. Topical chloramphenicol: use or abuse? Eye 1995;9:vii-viii.
Hall AV, Das SS, Tabaqchali S. Is it time to stop using chloramphenicol on the eye? Risk is low in short courses [Letter]. Br Med J 1995;311:450-1.
Sinclair NM, Leigh DA. A comparison of fusidic acid viscous eye drops and chloramphenicol eye ointment in acute conjunctivitis. Ther Res 1988;44:468-74.
Beasley H, Boltralik JJ, Baldwin HA. Chloramphenicol in aqueous humor after topical application. Arch Ophthalmol 1975;93:184-5.
Murugan N, Malathi J, Therese KL, Madhavan HN. Antimicrobial susceptibility and prevalence of extended-spectrum beta-lactamase (ESBL) and metallo beta-lactamase (MBL) and its co-exixtence among Pseudomonas aeruginosa recovered from ocular infections. Int J Pharm Pharm Sci 2015;7:147-51.
Kusuma SAF, Abdassah M, Valas BE. Formulation and evaluation of anti-acne gel containing Citrus aurantifolia juice using carbopol as a gelling agent. Int J Appl Pharm 2018;10:147-52.
Kusuma SAF, Agung MUK, Ismail AA. Antibacterial activity of extracellular compounds produced by bacterial exosymbion on sponges against Staphylococcus aureus ATCC 25923 Biofilm. J Pharm Sci Res 2017;9:1682-5.
Kusuma SAF, Yus Hargono CY, Hendro W. Beta-lactamase enzyme role in minimizing false-positive result of cefotaxime injection end-product sterility. J Pharm Sci Res 2018;10:1036-40.
Bartlett JD, Siret JD. Clinical ocular pharmacologi. 4th ed. Butterwort Heinemann; 2001.
Jitendra PK, Sharma A, Banik Dixit S. A new trend: ocular drug delivery system. Int J Pharm Sci 2011;2:1â€“25.
Lukas S. Formulasi steril. Penerbit ANDI, Yogyakarta; 2006.
Valldecabres MG, Alemany AL, Fiacle, Refojo MF. pH stability of ophthalmic solutions. Optometry 2004;75:161-8.
British Pharmacopoeia. Efficacy of antimicrobial preservation. Vol. IV. Appendix XVI C A367-A369. The Stationery Office, London; 2007.
Kotecha RK, Bhadra S, Rajesh KS. Formulation and process development of azithromycin ophthalmic nanosuspension. Int J Pharm Pharm Sci 2013;5:490-7.
Van Horn DL, Edelhauser HF, Prodanovich G, Eiferman R, Pederson HF. Effect of the ophthalmic preservative thimerosal on rabbit and human corneal endothelium. Invest Ophthalmol Vis Sci 1977;16:273-80.