Browse > Article
http://dx.doi.org/10.5762/KAIS.2019.20.2.681

The in-use stability study of multi-use ophthalmic solutions -Focused on Olopatadine, Fluorometholone, Dorzolamide, Timolol-  

Shin, Seo-young (School of Pharmacy, Sungkyunkwan University)
Jang, Kyoung won (Department of Pharmaceutical Quality, Daewon University College)
Sun, Sangouk (Department of Pharmaceutical Engineering, Dongshin University)
Ha, Dongmun (School of Pharmacy, Sungkyunkwan University)
Publication Information
Journal of the Korea Academia-Industrial cooperation Society / v.20, no.2, 2019 , pp. 681-693 More about this Journal
Abstract
Multi-use ophthalmic solutions are used many times after opening; therefore, there is a high possibility of decreased quality during use. This study was conducted to determine the recommended use period of multi-use ophthalmic solutions based on evaluation of the stability by comparing stability evaluation regulations of the USA, EU and Korea We selected four types of multi-use ophthalmic solutions (Olopatadine (Olo), Fluorometholone (Flu), Dorzolamide (Dor), Timolol (Timol)) that are frequently marketed in Korea and evaluated their stability during storage according to the actual usage method after opening. The Olo had a decrease in assay and preservative content at 2 months after opening, while Flu showed a significant difference from day 28 after opening. For Dor, significant differences were observed from day 14 after opening in the assay and impurity test item and Timol showed a significant difference from day 28 after opening. Based on the results of the stability test Olo and Flu should only be used within 28 days of opening, while Dor and Timol should be used within 14 days of opening. Therefore, we suggest that regulations system related use periods of multi-use ophthalmic solutions designed as aseptic preparations should be improved based on the results of stability tests after opening.
Keywords
multi-use ophthalmic solution; in-use stability; beyond-use date; sterile preparation; stability test;
Citations & Related Records
연도 인용수 순위
  • Reference
1 N. Sharma, S.S. Rao, A.M. Reddy, "A novel and rapid validated stability-indicating UPLC method of related substances for dorzolamide hydrochloride and timolol maleate in ophthalmic dosage form", J. Chromatogr. Sci, 50(9), 745-755, 2012. DOI: https://doi.org/10.1093/chromsci/bms025   DOI
2 S.P. Kulkarni, P.D. Amin, "Stability indicating HPTLC determination of timolol maleate as bulk drug and in pharmaceutical preparations", J. Pharm. Biomed. Anal, 23(6), 983-987, 2000. DOI: https://doi.org/10.1016/S0731-7085(00)00389-7   DOI
3 C. Rundfeldt, "Drug Development-A case study based insight into modern strategies (D. Mars, M. Birkhoff, "Multi-Dose Container for Nasal and Ophthalmic Drugs: A Preservative Free Future?)", Aptar Pharma, Consumer Healthcare Division, Germany, 509-524, 2011.
4 EZ-DRUG (https://ezdrug.mfds.go.kr/)
5 Korea consumer agency, "Analysis report of misuse eye-drop from misidentification of eye-drop", Korea, 2018 (http://www.kca.go.kr/brd/m_46/list.do)
6 K.H. Kim, J.R. Oh, J.H. Kim, H.M. Kim, "Bacteria-Filtering Effect of a Filtering System Used in Eye Drops", J Korean Ophthalmol Soc, 48(10), 1329-1334, 2007. DOI: https://doi.org/10.3341/jkos.2007.48.10.1329   DOI
7 B. Teuchner, J. Wagner, N.E. Bechrakis, D.O. Holler, M. Nagl, "Microbial Contamination of Glaucoma Eyedrops Used by Patients Compared With Ocular Medications Used in the Hospital", Journal Medicine, 94(8), 583-588, 2015 DOI: https://doi.org/10.1097/MD.0000000000000583   DOI
8 D.P. Freeman, M.Y. Kahook, "Preservatives in topical ophthalmic medications: historical and clinical perspectives", Expert Rev Ophthalmol, 4(1), 59-64, 2009. DOI: https://doi.org/10.1586/17469899.4.1.59   DOI
9 A. Tsegaw, T. Abula, Y. Assefa, "Bacterial Contamination of Multi-dose Eye Drops at Ophthalmology Department, University of Gondar, Northwest Ethiopia", Middle East Afr J Ophthalmol, 24(2), 81-86, 2017. DOI: https://doi.org/10.4103/meajo.MEAJO_308_16   DOI
10 Regulation on Pharmaceuticals Approval, Nortification and Review, MFDS, 2017.
11 R.B. Matthews, "Regulatory Aspects of Stability Testing in Europe", Drug Dev. Ind. Pharm, 25, 831-856, 1999. DOI: https://doi.org/10.1081/DDC-100102245   DOI
12 Danijela A. Kostic, Snezana S. Mitic, Danijela C. Naskovic, Aleksandra R. Zarubica, and Milan N. Mitic "Determination of Benzalkonium Chloride in Nasal Drops by High-Performance Liquid Chromatography", E-Journal of Chemistry, Volume 9, Issue 3, Pages 1599-1604, 2012. DOI: https://dx.doi.org/10.1155/2012/172070   DOI
13 L.M Jurkic, M. Buratovic, I. Valentic, D. Stanfel, "UHPLC study on the degradation profiles of olopatadine hydrochloride in eye drops subjected to heat and filtration methods of sterilisation", Chromatographia, 77, pp. 1067-1080, 2014. DOI: https://doi.org/10.1007/s10337-014-2712-y   DOI
14 Maha A. Hegazy, May H. Abdelwahab, Hassan A.M.Mendawy, Soheir A. Weshahy, Samah S. A bbas, "Validated HPTLC and HPLC methods for determination of fluorometholone and sodium crmoglycate in presence of their impurities and degradation products; application to kinetic study and on rabbit aqueous humor". J. Liquid chromatography & related technologies, 41(5), pp. 203-222, 2018. DOI: https://doi.org/10.1080/10826076.2018.1431926   DOI
15 Harry Brittain, "Analytical profiles of drug substancs and excipients 26th", Academic press, 1999.
16 MFDS(Ministry of Food and Drug Safety), "The Korean Pharmacopoeia (KP11)" [Annex 2], 6.1 ophthalmic solutions, Korea, 2018.
17 U.S. Pharmacopoeia National Formulary, USP General Chapters: <795> Pharmaceutical Compounding-Non sterile Preparations.
18 U.S. Pharmacopoeia National Formulary, USP General Chapters: <797> Pharmaceutical Compounding-sterile Preparations.
19 U.S. Pharmacopoeia National Formulary, USP General notice and requirements.
20 B.R. Matthews, G.M. Wall, "Stability Storage and Testing of Ophthalmic Products for Global Registration", Drug Dev. Ind. Pharm, 26(12), 1227-1237, 2000. DOI: https://doi.org/10.1081/DDC-100102304   DOI
21 S.D. Han, C.K. Kim, "Comparative Study on the Stability of Amoxicillin, Clavulanic Acid and its Commercial Combination Products", J. Pharm. Soc. Korea, 49(5), 392-398, 2005.
22 Guideline on Stability Testing for Pharmaceuticals after Opening, MFDS, 2016.
23 Shu Chiao Lin, Chin Fen Huang, Li Jiuan Shen, Hsueh Ju Wang, Chia Yu Lin, Fe Lin lin wu, "Formulation and stability of an extemporaneous 0.02% chlohexidine digluconate ophthalmic solution". Journal of the Formosan Medical Association, 2015; 114: 1162-1169, 2015. DOI: https://doi.org/10.1016/j.jfma.2014.08.003
24 M.J. Park, N.H. Joeng, "Stability evaluation of cefaclor dry syrup after opening with simulation design", J Oil Chemists Soc. Korea, 2017(3): 151-152, 2017.
25 Note for guidance on in-use stability testing of human medicinal products, EMA, 2001.
26 S. Bajaj, D. Signla, N. Sakhuja, "Stability Testing of Pharmaceutical Products", Journal of Applied Pharmaceutical Science, 02(03), 129-138, 2012.
27 R.T. Magari, E. Afonina, "In-use stability modeling", J. Pharm. Biomed. Anal, 56, 799-803, 2011. DOI: https://doi.org/10.1016/j.jpba.2011.07.004   DOI
28 B. Kommanaboyina, C.T. Rhodes, "Trends in Stability Testing, with Emphasis on Stability During Distribution and Storage", Drug Dev. Ind. Pharm, 25, 857-867, 1999. DOI: https://doi.org/10.1081/DDC-100102246   DOI
29 G.T. Kulkarni, G. Kuppusamy, B. Suresh, "Stability testing of pharmaceutical products: An overview", Indian J. Pharm. Educ, 38(4), 194-202, 2004.
30 K.C. Waterman, L. Chen, P. Waterman, B.C. Macdonald, A.P. Monahan, G. Scrivens, "Modeling of in-use stability for tablets and powders in bottles", Drug Dev. Ind. Pharm, 42(10), 1571-1578, 2016. DOI: https://doi.org/10.3109/03639045.2016.1153648   DOI
31 Y.H. Lee, "Microbial Contamination of Topical Eye Drugs", J Korean ophthalmol Soc. 37(5), 879-886, 1996.
32 N.R. Woo, N.J. Lee, S.J. Lee, M.Y. Kim, M.J. Park, J.P. Lee, W. Shin, "In-use Stability Study of Phloroglucinol and Nitroglycerin Sublingual Tablets Using Simulation Design after Opening of their Containers", Korean Journal of Pharm society, 61(6), pp. 281-285, 2017. DOI: https://doi.org/10.17480/psk.2017.61.6.281
33 E.Y. Tu, M.E. Shoff, W. Gao, C.E. Joslin, "Effect of low concentrations of benzalkonium chloride on acanthamoebal survival and its potential impact on empirical therapy of infectious keratitis", JAMA Ophthalmol, 131(5), 595-600, 2013. DOI: https://doi.org/10.1001/jamaophthalmol.2013.1644   DOI
34 M.Q. Rahman, D. Tejwani, J.A. Wilson, I. Butcher, K. Ramaesh, "Microbial contamination of preservative free eye drops in multiple application containers", Br. J. Ophthalmol, 90(2), 139-141, 2006. DOI: https://doi.org/10.1136/bjo.2005.078386   DOI