STERILITY AND STABILITY OF EXTEMPORANEOUS 0.01% ATROPINE EYE DROPS
Article Sidebar
Main Article Content
Abstract
PURPOSE: When commercial atropine eye drops are not available, diluted atropine eye drops are used for myopia control. However, long-term stability and sterility of self-prepared 0.01% atropine, even using aseptic techniques, are a concern. The purpose of this study was to investigate the sterility and stability of extemporaneously prepared 0.01% atropine sulfate (atropine) eye drops over a 90-day period.
METHODS: A 0.01% atropine solution was extemporaneously prepared by diluting commercially available 1% atropine eye drops with two artificial tear solutions, namely hydroxypropyl methylcellulose and polyethylene glycol. The preparations were stored at 4 °C and 25 °C. Sterility and stability were determined every month on days 0, 30, 60, and 90 after the solutions were prepared. For stability analysis, the amount of atropine was quantified using high performance liquid chromatography and comparing to that at day 0 (percentage of initial content). Bacterial and fungal cultures were performed to evaluate sterility.
RESULTS: No bacterial or fungal growth was observed during the study period. The 0.01% content of atropine prepared from hydroxypropyl methylcellulose at both 4 °C and 25 °C and polyethylene glycol kept at 4 °C remained constant, while that of atropine prepared in polyethylene glycol stored at 25 °C declined over time to approximately 20% of the initial amount.
CONCLUSIONS: The extemporaneous preparations of 0.01% atropine eye drops diluted from the concentrated commercial pharmaceutical product showed no microorganism growth after the 90-day storage period. However, preparations in different types of artificial tear solutions and storage temperatures can affect their stability.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Saw S-M, Gazzard G, Shih-Yen EC, Chua W-H. Myopia and associated pathological complications (Internet). Vol. 25, Ophthalmic and Physiological Optics. Wiley; 2005. p. 381–91. Available from: http://dx.doi.org/10.1111/j.1475-1313.2005.00298.x.
Rudnicka AR, Kapetanakis VV, Wathern AK, Logan NS, Gilmartin B, Whincup PH, et al. Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis: implications for aetiology and early prevention (Internet). Vol. 100, British Journal of Ophthalmology. BMJ; 2016. p. 882–90. Available from: http://dx.doi.org/10.1136/bjophthalmol-2015-307724
Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, et al. Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050 (Internet). Vol. 123, Ophthalmology. Elsevier BV; 2016. p. 1036–42. Available from: http://dx.doi.org/10.1016/j.ophtha.2016.01.006
Walline JJ, Lindsley K, Vedula SS, Cotter SA, Mutti DO, Twelker JD. Interventions to slow progression of myopia in children (Internet). Cochrane Database of Systematic Reviews. Wiley; 2011. Available from: http://dx.doi.org/10.1002/14651858.CD004916.pub3
Fan DSP, Lam DSC, Chan CKM, Fan AH, Cheung EYY, Rao SK. Topical Atropine in Retarding Myopic Progression and Axial Length Growth in Children with Moderate to Severe Myopia: A Pilot Study (Internet). Vol. 51, Japanese Journal of Ophthalmology. Springer Science and Business Media LLC; 2007. p. 27–33. Available from: http://dx.doi.org/10.1007/s10384-006-0380-7
Lee J-J, Fang P-C, Yang I-H, Chen C-H, Lin P-W, Lin S-A, et al. Prevention of Myopia Progression with 0.05% Atropine Solution (Internet). Vol. 22, Journal of Ocular Pharmacology and Therapeutics. Mary Ann Liebert Inc; 2006. p. 41–6. Available from: http://dx.doi.org/10.1089/jop.2006.22.41
Fang P-C, Chung M-Y, Yu H-J, Wu P-C. Prevention of Myopia Onset with 0.025% Atropine in Premyopic Children (Internet). Vol. 26, Journal of Ocular Pharmacology and Therapeutics. Mary Ann Liebert Inc; 2010. p. 341–5. Available from: http://dx.doi.org/10.1089/jop.2009.0135
SHIH Y-F, CHEN C-H, CHOU A-C, HO T-C, LIN LL-K, HUNG P-T. Effects of Different Concentrations of Atropine on Controlling Myopia in Myopic Children (Internet). Vol. 15, Journal of Ocular Pharmacology and Therapeutics. Mary Ann Liebert Inc; 1999. p. 85–90. Available from: http://dx.doi.org/10.1089/jop.1999.15.85
Yen MY, Liu JH, Kao SC, Shiao CH. Comparison of the effect of atropine and cyclopentolate on myopia. Ann Ophthalmol. 1989 May;21(5):180-2, 187.
Chua W-H, Balakrishnan V, Chan Y-H, Tong L, Ling Y, Quah B-L, et al. Atropine for the Treatment of Childhood Myopia (Internet). Vol. 113, Ophthalmology. Elsevier BV; 2006. p. 2285–91. Available from: http://dx.doi.org/10.1016/j.ophtha.2006.05.062
Chia A, Chua W-H, Cheung Y-B, Wong W-L, Lingham A, Fong A, et al. Atropine for the Treatment of Childhood Myopia: Safety and Efficacy of 0.5%, 0.1%, and 0.01% Doses (Atropine for the Treatment of Myopia 2) (Internet). Vol. 119, Ophthalmology. Elsevier BV; 2012. p. 347–54. Available from: http://dx.doi.org/10.1016/j.ophtha.2011.07.031
Shih Y-F, Hsiao CK, Chen C-J, Chang C-W, Hung PT, Lin LL-K. An intervention trial on efficacy of atropine and multi-focal glasses in controlling myopic progression (Internet). Vol. 79, Acta Ophthalmologica Scandinavica. Wiley; 2001. p. 233–6. Available from: http://dx.doi.org/10.1034/j.1600-0420.2001.790304.x
Liang C-K, Ho T-Y, Li T-C, Hsu W-M, Li T-M, Lee Y-C, et al. A combined therapy using stimulating auricular acupoints enhances lower-level atropine eyedrops when used for myopia control in school-aged children evaluated by a pilot randomized controlled clinical trial (Internet). Vol. 16, Complementary Therapies in Medicine. Elsevier BV; 2008. p. 305–10. Available from: http://dx.doi.org/10.1016/j.ctim.2008.04.007
Cooper J, Schulman E, Jamal N. Current status on the development and treatment of myopia. Optometry. 2012 May 31;83(5):179-99.
Li S-M, Wu S-S, Kang M-T, Liu Y, Jia S-M, Li S-Y, et al. Atropine Slows Myopia Progression More in Asian than White Children by Meta-analysis (Internet). Vol. 91, Optometry and Vision Science. Ovid Technologies (Wolters Kluwer Health); 2014. p. 342–50. Available from: http://dx.doi.org/10.1097/OPX.0000000000000178
Pineles SL, Kraker RT, VanderVeen DK, Hutchinson AK, Galvin JA, Wilson LB, et al. Atropine for the Prevention of Myopia Progression in Children (Internet). Vol. 124, Ophthalmology. Elsevier BV; 2017. p. 1857–66. Available from: http://dx.doi.org/10.1016/j.ophtha.2017.05.032
Yam JC, Jiang Y, Tang SM, Law AKP, Chan JJ, Wong E, et al. Low-Concentration Atropine for Myopia Progression (LAMP) Study (Internet). Vol. 126, Ophthalmology. Elsevier BV; 2019. p. 113–24. Available from: http://dx.doi.org/10.1016/j.ophtha.2018.05.029
Chia A, Lu Q-S, Tan D. Five-Year Clinical Trial on Atropine for the Treatment of Myopia 2 (Internet). Vol. 123, Ophthalmology. Elsevier BV; 2016. p. 391–9. Available from: http://dx.doi.org/10.1016/j.ophtha.2015.07.004
Chia A, Chua W-H, Wen L, Fong A, Goon YY, Tan D. Atropine for the Treatment of Childhood Myopia: Changes after Stopping Atropine 0.01%, 0.1% and 0.5% (Internet). Vol. 157, American Journal of Ophthalmology. Elsevier BV; 2014. p. 451-457.e1. Available from: http://dx.doi.org/10.1016/j.ajo.2013.09.020
Moon JS, Shin SY. The diluted atropine for inhibition of myopia progression in Korean children. Int J Ophthalmol. 2018;11(10):1657-62.
Saito J, Imaizumi H, Yamatani A. Physical, chemical, and microbiological stability study of diluted atropine eye drops (Internet). Vol. 5, Journal of Pharmaceutical Health Care and Sciences. Springer Science and Business Media LLC; 2019. Available from: http://dx.doi.org/10.1186/s40780-019-0154-2