• SRI AGUNG FITRI KUSUMA Department of Biology Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, Indonesia 45363
  • MARLINE ABDASSAH Departement of Pharmaceutics, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, Indonesia 45363
  • FITASARY MARYATI Departement of Pharmaceutics, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, Indonesia 45363



Eye drops, Chloramphenicol, Thimerosal, Benzalkonium chloride, Benzyl alcohol


Objective: The aim of this study was to compare the preservative efficacy of benzalkonium chloride, thimerosal and benzyl alcohol in eye drops formulation containing chloramphenicol as the active agents for producing the sterile and effective eye drops.Methods: The efficacy of preservatives was assayed by evaluating the physical appearance, pH stability, sterility and the antibacterial effectivity of the formulated eye drops. Each of 0.5% chloramphenicol was formulated with different preservatives of benzalkonium chloride, thimerosal and benzyl alcohol at its recommended concentration, 0.01%; 0.01% and 1%, respectively. The in vitro stability was examined periodically for the eye drops formulation stored at room temperature during the 28-day period. The effectiveness of the antibacterial effect of chloramphenicol in eye drops was assayed by using the agar diffusion method against Escherichia coli and evaluated for the diameter of inhibition zones. Result: The clarity of the eye drops formula produced clear solutions. The eye drops formula exhibited relatively stabile on pH. All the formulated eye drops were sterile during the storage time. The appropriate of the sterilization method was thought to contribute to the sterility of eye drops which did not contain preservatives. In addition, it was assumed that the pre-reaction of chloramphenicol in inhibiting the contaminants in the eye drop may occur during the storage time. This hypothesis was confirmed by the inhibitory diameter stability produced by the eye drop formulas containing preservatives compared to that of not. The decrease in inhibition diameter occurred during the storage period (28 d) of each formula was as follows: F0 (51.58%), F1 (35.76%), F2 (31.86%), and F3 (35.35%). The best stability based on the antibacterial activity of the chloramphenicol eye drops was produced by F2 which used 0.01% thimerosal as its preservative. The differences in inhibition diameter were significantly influenced by the presence and the type of preservatives.

Conclusion: 0.01% thimerosal indicated the best improvement on the efficacy of 0.5% chloramphenicol eye drop.


Download data is not yet available.


Beal C, Giordano B. Clinical evaluation of red eyes in pediatric patients. J Pediatr Health Care 2016;30:506-14.

Azari AA, Barney NP. Conjunctivitis: a systematic review of diagnosis and treatment. JAMA 2013;310:1721-9.

Epling J. Bacterial conjunctivitis. Br Med J Clin Evid 2012;2:1-21.

Limberg MB. A review of bacterial keratitis and bacterial conjunctivitis. Am J Ophthalmol 1991;112:2S–9S.

Thadani SM, Foster CS. Treatment of ocular inflammation in children. Pediatr Drugs 2004;6:289–301.

Høvding G. Acute bacterial conjunctivitis. Acta Ophthalmol 2008;86:5-17.

Feghhi M, Mahmoudabadis AZ, Mehdinejad M. Evaluation of fungal and bacterial contaminations of patient-used ocular drops. Med Mycol 2008;46:17-21.

Patel PB, Diaz MC, Bennett JE, Attia MW. Clinical features of bacterial conjunctivitis in children. Acad Emerg Med 2007;14:1-5.

Rietveld RP, Ter Riet G, Bindels PJ, Sloos JH, Van Weert HC. Predicting bacterial cause in infectious conjunctivitis: cohort study on informativeness of combinations of signs and symptoms. Br Med J 2004;329:206-10.

Sheikh A, Hurwitz B. Antibiotics versus placebo for acute bacterial conjunctivitis. Cochrane Database Syst Rev 2006;4:CD001211.

Peneva PT. Non-steroidal anti-inflammatory drugs for topical ophthalmic administration: contemporary trends. Int J Pharm Pharm Sci 2015;7:13-9.

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;9:7-8.

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.

WHO. Blindness and vision impairment prevention. WHO, Geneva; 2020.

Tsegaw A, Abula T, Assefa Y. Bacterial contamination of multi-dose eye drops at ophthalmology department, University of Gondar, Northwest Ethiopia. Middle East Afr J Ophthalmol 2017;24:81–6.

Taşli H, Coşar G. Microbial contamination of eye drops. Cent Eur J Public Health 2001;9:162-4.

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.

Baird RM. Guide to microbiological control in pharmaceuticals. CRC Press, New York; 2007.

Noecker R. Effects of common ophthalmic preservatives on ocular health. R Adv Ther 2001;18:205-15.

Klein M, Millwood EG. On the sterility of eye ointments. Br J Ophthal 1964;48:285-7.

Yi Sheng C, Chiou Feng L, Chao Liang W, Pao Ying K, Fong Sen W, Chi Chang S, et al. Mechanisms underlying benzyl alcohol cytotoxicity (triamcinolone acetonide preservative) in human retinal pigment epithelial cells. Invest Ophth Vis Sci 2011;52:4214-22.

Abdassah M, Kusuma SAF. Comparison of thimerosal effectiveness in the formulation of eye drops containing neomycin sulfate and chloramphenicol. Int J Appl Pharm 2019;11:130-5.

Kusuma SAF, Hargono Y, Winarno H. Betalactamase enzyme role in minimizing false-positive result of cefotaxime injection end-product sterility. J Pharm Sci Res 2018;10:1036-40.

Sudjana MA. Metode statistika. 8th ed. Penerbit Tarsito, Bandung; 2002.

Shih IK. Photodegradation products of chloramphenicol in aqueous solution. J Pharm Sci 1971;60:1889-90.

Jitendra, Sharma PK, Banik A, Dixit S. A new trend: ocular drug delivery system. Int J Pharm Sci 2011;2:1–25.

Lukas S. Formulasi Steril. Penerbit ANDI, Yogyakarta; 2006.

British Pharmacopoeia. Efficacy of antimicrobial preservation. Vol. IV. Appendix XVI C A367-A369. The Stationery Office, London; 2007.

Kallings L, Rigertz O, Silverstolpe I. Microbial contamination of medical preparations. Acta Pharm Sue 1966;3:199–213.

Furrer P, Mayer JM, Gurny R. Ocular tolerance of preservatives and alternatives. Eur J Pharm Biopharm 2002;53:263-80.

Rahman MQ, Tejwani D, Wilson JA, Butcher I, Ramaesh K. Microbial contamination of preservative free eye drops in multiple application containers. Br J Ophthalmol 2006;90:139-41.

Bartlett JD, Siret JD. Clinical ocular pharmacologi. 4th ed. Butterwort Heinemann; 2001.

Nelson L, Goldfrank L. Goldfrank's toxicologic emergencies. 9th ed. McGraw-Hill Medical; 2011.

Croshaw B. Preservatives for cosmetics and toiletries. J Soc Cosmet Chem 1977;28:3–16.

Karabit MS, Juneskans OT, Lundgren P. Studies on the evaluation of preservative efficacy II: the determination of antimicrobial characteristics of benzyl alcohol. J Clin Hosp Pharm 1986;11:281–9.

Shah AK, Simons KJ, Briggs CJ. Physical, chemical, and bioavailability studies of parenteral diazepam formulations containing propylene glycol and polyethylene glycol 400. Drug Dev Ind Pharm 1991;17:1635–54.

Wallhausser KH. Benzyl alcohol. Kabara JJ. ed. Cosmetic and drug preservation principles and practice. Marcel Dekker, New York; 1984.

Meyer BK, Ni A, Hu B, Shi L. Antimicrobial preservative use in parenteral products: past and present. J Pharm Sci 2007;96:3155–67.

Saisyo A, Oie S, Kimura K, Sonoda KH, Furukawa H. Microbial contamination of in-use ophthalmic preparations and its prevention. Bull Yamaguchi Med Sch 2016;63:17-24.

Bachewar NP, Deshmukh D, Choudhari SR, Joshi RS. Evaluation of used eye drop containers for microbial contamination in outpatient department of tertiary care teaching hospital. Int J Basic Clin Pharmacol 2018;7:895-9.

Jithan V, Mohan CK, Vimaladevi M. Development and evaluation of a chloramphenicol hypertonic ophthalmic solution. Indian J Pharm Sci 2008;70:66–70.

Fassihi RA. Preservation of medicines against microbial contamination. In: SA Block. Ed. Disinfection Sterilization and Preservation. 4th Ed. Lea and Febiger; 1991.

Hugo WB, Russell AD. Pharmaceutical microbiology. 6thEd. Blackwell Science; 1998.

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.

Kibbe AH. Benzalkonium chloride monograph. In: Rowe RC, Sheskey PJ, Weller PJ. Handbook of Pharmaceutical Excipients. 5th ed. Pharmaceutical Press; 2006.

Cahill E. Benzyl alcohol monograph. In: Rowe RC, Sheskey PJ, Weller PJ. Handbook of Pharmaceutical Excipients. 5th ed. Pharmaceutical Press; 2006.



How to Cite




Original Article(s)

Most read articles by the same author(s)

<< < 1 2 3 > >>