{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T04:17:09Z","timestamp":1761365829161,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Progressive myopia in children is a highly prevalent condition in societies worldwide and is often treated with compounded low-dose atropine sulfate (AS) eye drops without preserving agents to avoid irritation\/sensitisation. Surprisingly, there is a lack of data regarding the in-use stability of contamination-free LDPE dispenser units (CFDs) for this compounded multidose product, which causes uncertainty among prescribers and patients in Europe. Thus, our aim was to compare the effect of different dispenser types on the chemical and microbial stability of unpreserved AS eye drops (0.01% w\/w). A dripping simulation was performed to obtain information on microbial stability over 4 weeks through plating and separately over 12 weeks through direct inoculation, HPLC and pH analysis. For CFDs, no contamination was found after 4, 8 or 12 weeks of use when stored at 23 or 4 \u00b0C as opposed to the control. AS content remained within 0.01 \u00b1 0.0002% w\/w after 12 weeks, with higher chemical stability at 4 \u00b0C despite decreasing pH. A stress test confirmed the validity of the CFD system. In conclusion, using CFDs and refrigerated storage was found to be safe for compounded unpreserved AS eye drops over 12 weeks of use.<\/jats:p>","DOI":"10.3390\/life15111646","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:14:02Z","timestamp":1761182042000},"page":"1646","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbial and Chemical Stability of Unpreserved Atropine Sulfate 0.01% w\/w Eye Drops\u2014A Pilot Study on the Impact of Dispenser Type and Storage Temperature over 12 Weeks of Daily Use After Compounding"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2561-4378","authenticated-orcid":false,"given":"Victoria","family":"Klang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Brenner","sequence":"additional","affiliation":[{"name":"Laboratory of the Austrian Pharmacy Chamber Vienna, Spitalgasse 31, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Grabner","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Unzeitig","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6548-1784","authenticated-orcid":false,"given":"My Vanessa","family":"Nguyen Hoang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, 1090 Vienna, Austria"},{"name":"Vienna Doctoral School of Pharmaceutical, Nutritional and Sport Sciences, University of Vienna, Josef-Holaubek-Platz 2, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Lummerstorfer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, 1090 Vienna, Austria"},{"name":"Vienna Doctoral School of Pharmaceutical, Nutritional and Sport Sciences, University of Vienna, Josef-Holaubek-Platz 2, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Pichler","sequence":"additional","affiliation":[{"name":"Laboratory of the Austrian Pharmacy Chamber Vienna, Spitalgasse 31, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Steiner","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3625-4654","authenticated-orcid":false,"given":"Richard D.","family":"Harvey","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","first-page":"139","article-title":"On the Atropine Treatment of Acquired and Progressive Myopia","volume":"2","author":"Derby","year":"1874","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_2","first-page":"78","article-title":"Topical Atropine in the Control of Myopia","volume":"5","author":"Galvis","year":"2016","journal-title":"Med. Hypothesis Discov. Innov. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.ophtha.2023.02.020","article-title":"Efficacy in Myopia Control: The Low-Concentration Atropine for Myopia Progression (LAMP) Study","volume":"130","author":"Bullimore","year":"2023","journal-title":"Ophthalmology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Myles, W., Dunlop, C., and McFadden, S.A. (2021). The Effect of Long-Term Low-Dose Atropine on Refractive Progression in Myopic Australian School Children. J. Clin. Med., 10.","DOI":"10.3390\/jcm10071444"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1136\/bjo-2023-324615","article-title":"Efficacy of weekly dose of 1% atropine for myopia control in Chinese children","volume":"109","author":"Du","year":"2024","journal-title":"Br. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1007\/s10792-020-01356-x","article-title":"Part-time use of 1% atropine eye drops for prevention of myopia progression in children","volume":"40","author":"Foo","year":"2020","journal-title":"Int. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ophtha.2011.07.031","article-title":"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)","volume":"119","author":"Chia","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1186\/s12886-023-03177-9","article-title":"Safety and efficacy of 0.01% and 0.1% low-dose atropine eye drop regimens for reduction of myopia progression in Danish children: A randomized clinical trial examining one-year effect and safety","volume":"23","author":"Hansen","year":"2023","journal-title":"BMC Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/aos.16604","article-title":"Preservatives and pH in low-dose atropine formulations for clinical trials","volume":"102","author":"Iribarren","year":"2024","journal-title":"Acta Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1358046","DOI":"10.3389\/fmed.2024.1358046","article-title":"Effect of 0.01% atropine combined with orthokeratology lens on axial elongation: A 2-year randomized, double-masked, placebo-controlled, cross-over trial","volume":"11","author":"Li","year":"2024","journal-title":"Front. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1186\/s13104-022-06240-8","article-title":"Hospital-prepared low-dose atropine eye drops for myopia progression control using atropine sulfate injection diluted in normal saline and lubricants","volume":"15","author":"Wongwirawat","year":"2022","journal-title":"BMC Res. Notes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.ophtha.2024.03.013","article-title":"Five-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression (LAMP) Study: Phase 4 Report","volume":"131","author":"Zhang","year":"2024","journal-title":"Ophthalmology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s40780-019-0154-2","article-title":"Physical, chemical, and microbiological stability study of diluted atropine eye drops","volume":"5","author":"Saito","year":"2019","journal-title":"J. Pharm. Health Care Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1177\/11206721241229317","article-title":"Effects of atropine eyedrops at ten different concentrations for myopia control in children: A systematic review on meta-analysis","volume":"34","author":"Wang","year":"2024","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4274572","DOI":"10.1155\/2021\/4274572","article-title":"Efficacy and Adverse Effects of Atropine for Myopia Control in Children: A Meta-Analysis of Randomised Controlled Trials","volume":"2021","author":"Chen","year":"2021","journal-title":"J. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1001\/jamaophthalmol.2017.1091","article-title":"Efficacy and Adverse Effects of Atropine in Childhood Myopia: A Meta-analysis","volume":"135","author":"Gong","year":"2017","journal-title":"JAMA Ophthalmol."},{"key":"ref_17","unstructured":"(2014). Water Quality\u2014Enumeration of Escherichia coli and Coliform bacteria\u2014Part 1: Membrane Filtration Method for Waters with Low Bacterial Background Flora (Standard No. ISO 9308-1:2014)."},{"key":"ref_18","unstructured":"(2014). Microbiology of Food, Animal Feed and Water\u2014Preparation, Production, Storage and Performance Testing of Culture Media (Standard No. ISO 11133:2014)."},{"key":"ref_19","unstructured":"(2019). Cosmetics\u2014Microbiology\u2014Evaluation of the Antimicrobial Protection of a Cosmetic Product (Standard No. ISO 11930:2019)."},{"key":"ref_20","unstructured":"(2017). Cosmetics\u2014Microbiology\u2014Detection of Specified and Non-Specified Microorganisms (Standard No. ISO 18415:2017)."},{"key":"ref_21","unstructured":"(2015). Cosmetics\u2014Microbiology\u2014Detection of Candida albicans (Standard No. ISO 18416:2015)."},{"key":"ref_22","unstructured":"(2017). Cosmetics\u2014Microbiology\u2014Enumeration and Detection of Aerobic Mesophilic Bacteria (Standard No. ISO 21149:2017)."},{"key":"ref_23","unstructured":"(2015). Cosmetics\u2014Microbiology\u2014Detection of Escherichia coli (Standard No. ISO 21150:2015)."},{"key":"ref_24","unstructured":"(2015). Cosmetics\u2014Microbiology\u2014Detection of Pseudomonas aeruginosa (Standard No. ISO 22717:2015)."},{"key":"ref_25","unstructured":"(2015). Cosmetics\u2014Microbiology\u2014Detection of Staphylococcus aureus (Standard No. ISO 22718:2015)."},{"key":"ref_26","unstructured":"(2017). Cosmetics\u2014Microbiology\u2014Enumeration of Yeast and Mould (Standard No. ISO 16212:2017)."},{"key":"ref_27","unstructured":"(2017). Microbiology of the Food Chain\u2014Horizontal Method for the Detection of Pathogenic Yersinia Enterocolitica (Standard No. ISO 10273:2017)."},{"key":"ref_28","unstructured":"(2006). Microbiology of Food and Animal Feeding Stuffs\u2014Horizontal Method for the Determination of Low Numbers of Presumptive Bacillus Cereus\u2014Most Probable Number Technique and Detection Method (Standard No. ISO 21871:2006)."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Vicario-de-la-Torre, M., Puebla-Garcia, V., Ybanez-Garcia, L., Lopez-Cano, J.J., Gonzalez-Cela-Casamayor, M.A., Brugnera, M., Burgos-Blasco, B., Diaz-Valle, D., Gegundez-Fernandez, J.A., and Benitez-Del-Castillo, J.M. (2024). Topical Insulin Eye Drops: Stability and Safety of Two Compounded Formulations for Treating Persistent Corneal Epithelial Defects. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16050580"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e0316122","DOI":"10.1128\/spectrum.03161-22","article-title":"Improvement of the Pour Plate Method by Separate Sterilization of Agar and Other Medium Components and Reduction of the Agar Concentration","volume":"11","author":"Casino","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_31","first-page":"1247","article-title":"Microbial integrity test for preservative-free multidose eyedroppers or nasal spray pumps","volume":"81","author":"Marx","year":"2019","journal-title":"Pharm. Ind."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.ejpb.2003.10.009","article-title":"Extension of in-use stability of preservative-free nasalia","volume":"57","author":"Bagel","year":"2004","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Freiberg, J.C., Hedengran, A., Heegaard, S., Petrovski, G., Jacobsen, J., Cvenkel, B., and Kolko, M. (2022). An Evaluation of the Physicochemical Properties of Preservative-Free 0.005% (w\/v) Latanoprost Ophthalmic Solutions, and the Impact on In Vitro Human Conjunctival Goblet Cell Survival. J. Clin. Med., 11.","DOI":"10.3390\/jcm11113137"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1007\/s40123-022-00482-2","article-title":"In Vitro and In-Eye Comparison of Commercial Pilocarpine Ophthalmic Solution and an Optimized, Reformulated Pilocarpine for Presbyopia Treatment","volume":"11","author":"Jackson","year":"2022","journal-title":"Ophthalmol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0022-0728(92)80571-K","article-title":"Investigations of hydrolysis kinetics of atropine sulphate by electroanalysis at the water\/nitrobenzene interface","volume":"334","author":"Wang","year":"1992","journal-title":"J. Electroanal. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1097\/ICL.0000000000000932","article-title":"Compounding of Low-Concentration Atropine for Myopia Control","volume":"48","author":"Richdale","year":"2022","journal-title":"Eye Contact Lens"},{"key":"ref_37","unstructured":"Tan-Lhernould, L., Jobard, M., Brandely-Piat, M.-L., and Batista, R. (2020, January 23\u201324). Could we package atropine eye drops 0.1 and 0.5 mg\/mL in Novelia\u00ae bottles?. Proceedings of the 2\u00e8mes Journ\u00e9es du GERPAC, Virtual Meeting."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/11\/1646\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T04:13:33Z","timestamp":1761365613000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/11\/1646"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,22]]},"references-count":37,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["life15111646"],"URL":"https:\/\/doi.org\/10.3390\/life15111646","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2025,10,22]]}}}