{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:16:19Z","timestamp":1786122979138,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Meropenem is a broad-spectrum carbapenem antibiotic with demonstrated efficacy against multidrug-resistant Gram-negative pathogens. Although its use as an ophthalmic formulation is off-label, growing clinical evidence supports its application in severe ocular infections such as keratitis and endophthalmitis. However, the intrinsic instability of meropenem in aqueous solutions and the absence of standardized ophthalmic preparations limit its routine use. Furthermore, no stability studies are currently available for meropenem 50 mg\/mL eye drops stored in polypropylene (PP) dropper bottles under freezing and subsequent refrigerated conditions. The aim of this study was to evaluate the physicochemical and microbiological stability of a 50 mg\/mL meropenem ophthalmic solution prepared in a hospital pharmacy using a commercial meropenem pharmaceutical product, and packaged in PP containers. Methods: Eye drops were aseptically prepared from a commercially available pharmaceutical product, containing 1g de meropenem and anhydrous sodium carbonate as an excipient. After preparation, the drops were stored at \u221220 \u00b1 2 \u00b0C for up to 42 days, followed by refrigerated storage (5 \u00b1 3 \u00b0C) after thawing for up to 7 days. Chemical stability was assessed using a validated stability-indicating HPLC method in accordance with ICH guidelines and was defined as 90\u2013110% recovery of the initial concentration. Physical stability (appearance, pH, particulate matter) and microbiological stability were also evaluated under simulated in-use conditions. Results: The HPLC method demonstrated excellent linearity, precision, and accuracy. Meropenem concentrations remained within the predefined acceptance limits throughout the 42-day study period under freezing conditions, with no significant changes in pH, color, or particulate formation. After thawing, a progressive decrease in drug concentration was observed under refrigerated conditions, falling below 90% of the initial concentration within 24\u201348 h. A concomitant color change from colorless to yellow was also detected, consistent with \u03b2-lactam ring hydrolysis. Despite this degradation, no significant changes in physical parameters other than color were observed, and microbiological testing confirmed sterility for up to 7 days under refrigerated conditions. Conclusions: Meropenem drops 50 mg\/mL in PP dropper bottles are physicochemically and microbiologically stable for 43 days (42 days under frozen conditions plus 1 day, in-use conditions, after opening and under refrigeration).<\/jats:p>","DOI":"10.3390\/pharmaceutics18080971","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T13:20:16Z","timestamp":1786108816000},"page":"971","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stability Study of Meropenem 50 mg\/mL Eye Drops in Polypropylene Dropper Bottles"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4247-8942","authenticated-orcid":false,"given":"Juan Carlos Ruiz","family":"Ramirez","sequence":"first","affiliation":[{"name":"Pharmacy Service, Los Arcos del Mar Menor University General Hospital, Murcian Health Service, San Javier, 30739 Murcia, Spain"},{"name":"Department of Pharmacology, Faculty of Pharmacy, CEIR Campus Mare Nostrum (CMN), University of Murcia, 30120 Murcia, Spain"},{"name":"Biomedical Research Institute of Murcia Pascual Parrilla\u2014IMIB, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Encarnaci\u00f3n Mart\u00ednez","family":"Madrid","sequence":"additional","affiliation":[{"name":"Pharmacy Service, Santa Luc\u00eda University General Hospital, Murcian Health Service, Cartagena, 30202 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e1n G\u00f3miz","family":"S\u00e1ez","sequence":"additional","affiliation":[{"name":"Pharmacy Service, Virgen de la Salud\u2014Elda General Hospital, Valencian Health Service, Elda, 03600 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice Charlotte","family":"Viney","sequence":"additional","affiliation":[{"name":"Pharmacy Service, Los Arcos del Mar Menor University General Hospital, Murcian Health Service, San Javier, 30739 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7520-1132","authenticated-orcid":false,"given":"Jos\u00e9 Mar\u00eda Alonso","family":"Herreros","sequence":"additional","affiliation":[{"name":"Pharmacy Service, Los Arcos del Mar Menor University General Hospital, Murcian Health Service, San Javier, 30739 Murcia, Spain"},{"name":"Department of Pharmacology, Faculty of Pharmacy, CEIR Campus Mare Nostrum (CMN), University of Murcia, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1576-7760","authenticated-orcid":false,"given":"Pilar Almela","family":"Rojo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, CEIR Campus Mare Nostrum (CMN), University of Murcia, 30120 Murcia, Spain"},{"name":"Biomedical Research Institute of Murcia Pascual Parrilla\u2014IMIB, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref_1","unstructured":"European Pharmacopoeia Commission (2024). Monograph: Meropenem Trihydrate. Eur Pharmacopoeia, European Directorate for the Quality of Medicines & HealthCare. [11th ed.]."},{"key":"ref_2","unstructured":"Kern Pharma, S.L. (2012). Datasheet Meropenem Kern Pharma 1000 mg Powder for Inyectable Solution EFG, Kern Pharma, S.L.. Available online: https:\/\/cima.aemps.es\/cima\/dochtml\/ft\/76308\/FT_76308.html."},{"key":"ref_3","unstructured":"Goodman, L., Gilman, A., Brunton, L., Hilal-Dandan, R., and Knollmann, B. (2023). Goodman & Gilman: Las Bases Farmacol\u00f3gicas de la Terap\u00e9utica, McGraw Hill Medical. [14th ed.]. Available online: https:\/\/accessmedicina.mhmedical.com\/book.aspx?bookid=3218."},{"key":"ref_4","unstructured":"Ministerio de Sanidad y Pol\u00edtica Social (2026, April 29). Real Decreto 1015\/2009, de 19 de Junio, por el que se Regula la Disponibilidad de Medicamentos en Situaciones Especiales. Sect. 1, Real Decreto 1015\/2009 20 July 2009; pp. 60904\u201360913. Available online: https:\/\/www.boe.es\/eli\/es\/rd\/2009\/06\/19\/1015."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e33916","DOI":"10.1016\/j.heliyon.2024.e33916","article-title":"In-vitro safety assessment of meropenem on human retinal pigment epithelium (RPE)","volume":"10","author":"Hoseini","year":"2024","journal-title":"Heliyon"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4103\/2320-3897.122637","article-title":"Use of topical meropenem in management of hospital acquired Pseudomonas ocular infections","volume":"2","author":"Pande","year":"2014","journal-title":"J. Clin. Ophthalmol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5731","DOI":"10.1167\/iovs.15-17077","article-title":"Pharmacokinetics of Meropenem for Use in Bacterial Keratitis","volume":"56","author":"Sueke","year":"2015","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1097\/ICL.0000000000000745","article-title":"A New Treatment Experience in Pseudomonas Keratitis: Topical Meropenem and Cefepime","volume":"47","author":"Bozkurt","year":"2021","journal-title":"Eye Contact Lens"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12348-023-00363-0","article-title":"Successful treatment of multidrug-resistant Pseudomonas aeruginosa keratitis with meropenem eye drops\u2014A case report","volume":"13","author":"Elhardt","year":"2023","journal-title":"J. Ophthalmic Inflamm. Infect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1167\/iovs.09-4638","article-title":"Minimum inhibitory concentrations of standard and novel antimicrobials for isolates from bacterial keratitis","volume":"51","author":"Sueke","year":"2010","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"bcr2018225163","DOI":"10.1136\/bcr-2018-225163","article-title":"The successful treatment of a multidrug-resistant Achromobacter xylosoxidans corneal ulcer with topical meropenem","volume":"2018","author":"Tavassoli","year":"2018","journal-title":"BMJ Case Rep."},{"key":"ref_12","first-page":"336","article-title":"Comparison of Intravitreal Ceftazidime and Meropenem in Treatment of Experimental Pseudomonal Posttraumatic Endophthalmitis in a Rabbit Model","volume":"4","author":"Manav","year":"2004","journal-title":"J. Appl. Res."},{"key":"ref_13","first-page":"e81977","article-title":"Rare and in Your Chair: An Emerging Use of Meropenem in a Case of Klebsiella pneumoniae Endophthalmitis Following Cataract Surgery","volume":"17","author":"Ong","year":"2025","journal-title":"Cureus"},{"key":"ref_14","first-page":"1364","article-title":"Revisiting systemic treatment of bacterial endophthalmitis: A review of intravitreal penetration of systemic antibiotics","volume":"25","author":"Brockhaus","year":"2019","journal-title":"Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1089\/jop.1999.15.439","article-title":"Penetration and decay of meropenem into the human aqueous humor and vitreous","volume":"15","author":"Schauersberger","year":"1999","journal-title":"J. Ocul. Pharmacol. Ther. Off. J. Assoc. Ocul. Pharmacol. Ther."},{"key":"ref_16","first-page":"73","article-title":"Estabilidad fisicoqu\u00edmica y microbiol\u00f3gica de un colirio de insulina 10 UI\/mL","volume":"34","year":"2024","journal-title":"Rev. OFIL. Organ. De Farm. Ibero-Latinoam."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.farma.2024.01.007","article-title":"Estudio de estabilidad fisicoqu\u00edmica y microbiol\u00f3gica de dos nuevos colirios de metilprednisolona sin conservantes","volume":"48","year":"2024","journal-title":"Farm. Hosp."},{"key":"ref_18","unstructured":"D\u00e1vila Pousa, C., Alonso Herreros, J.M., Berisa Prado, S., Ca\u00f1ete Ram\u00edrez, C., Feal Cortizas, B., Flox Ben\u00edtez Mdel, P., Fuentes Irigoyen, R., Garc\u00eda Palomo, M., L\u00f3pez Cabezas, C., and Mart\u00edn de Rosales Cabrera, A.M. (2023). Manual de Farmacotecnia, SEFH (Sociedad Espa\u00f1ola de Farmacia Hospitalaria)."},{"key":"ref_19","first-page":"48","article-title":"Estabilidad y esterilidad de un colirio de fenilefrina al 2.5%","volume":"23","year":"1998","journal-title":"Farm Hosp."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/1752-153X-7-98","article-title":"Solid-state stability study of meropenem\u2014Solutions based on spectrophotometric analysis","volume":"7","author":"Paczkowska","year":"2013","journal-title":"Chem. Cent. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e53","DOI":"10.1136\/ejhpharm-2018-001699","article-title":"Investigation of meropenem stability after reconstitution: The influence of buffering and challenges to meet the NHS Yellow Cover Document compliance for continuous infusions in an outpatient setting","volume":"27","author":"Jamieson","year":"2020","journal-title":"Eur. J. Hosp. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13608","DOI":"10.1038\/s41598-019-49264-0","article-title":"Mechanistic Insights into \u03b2-Lactamase-Catalysed Carbapenem Degradation Through Product Characterisation","volume":"9","author":"Lohans","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","first-page":"e02064-23","article-title":"Stability of meropenem in portable elastomeric infusion devices: Which protocol should be implemented in clinical practice?","volume":"12","author":"Serrano","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1177\/0018578718779009","article-title":"Stability of Meropenem After Reconstitution for Administration by Prolonged Infusion","volume":"54","author":"Fawaz","year":"2019","journal-title":"Hosp. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.2147\/DDDT.S212052","article-title":"An investigation of the stability of meropenem in elastomeric infusion devices","volume":"13","author":"Foy","year":"2019","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ijpharm.2007.08.023","article-title":"Thermal and alkaline stability of meropenem: Degradation products and cytotoxicity","volume":"350","author":"Mendez","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_27","first-page":"27","article-title":"Oxygen Permeability in Food Packaging made of Polypropylene by Injection Moldin","volume":"53","year":"2024","journal-title":"Rev. Polit\u00e9cnica. Esc. Polit\u00e9cnica Nac."},{"key":"ref_28","first-page":"587","article-title":"Interacci\u00f3n de f\u00e1rmacos y mezclas parenterales con productos sanitarios","volume":"11","year":"2020","journal-title":"Panor. Actual Medicam."},{"key":"ref_29","unstructured":"Laboratorios Grifols, SA (2025, August 01). Estabilidad y Compatibilidad de Medicamentos [Internet]. Available online: https:\/\/gruposdetrabajo.sefh.es\/gps\/images\/stories\/descargas\/Compatibilidad_medicamentos_diluyentes.pdf."},{"key":"ref_30","unstructured":"Ministry of Health (2025, August 01). Guideline for Good Practices for Preparing Medications in Hospital Pharmacy Services, Available online: https:\/\/www.sanidad.gob.es\/areas\/farmacia\/publicaciones\/GuiaBPMedicamentosServFarmHosp\/Docs\/04GuiaMedicamentos2024Accesible.pdf."},{"key":"ref_31","unstructured":"European Directorate for the Quality of Medicines & HealthCare (2022). European Pharmacopoeia, European Directorate for the Quality of Medicines & HealthCare. [11th ed.]."},{"key":"ref_32","unstructured":"United States Pharmacopeial Convention (2022). United States Pharmacopeia and National Formulary (USP-NF), US Pharmacopeia Convention, Inc.. [2022nd ed.]."},{"key":"ref_33","unstructured":"Castro, M., Gasc\u00f3n, S., Pujol, M., Sans, J., and Vicente, L. (1989). Validation of Analytical Methods, Spanish Association of Industrial Pharmacists (AEFI). Monograph; Commission on Good Manufacturing Practice and Quality Control Standards."},{"key":"ref_34","first-page":"441","article-title":"Method development and validation of meropenem in pharmaceutical dosage form by RP-HPLC","volume":"24","author":"Negi","year":"2017","journal-title":"Indian J. Chem. Tecnol."},{"key":"ref_35","unstructured":"Brouder, A., and Tietje, C. (2009). International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Handb Transnatl Econ Gov Regimes, Brill."},{"key":"ref_36","unstructured":"Hoffman, F. (1987). Statistical Validation: Quantitative Determination (General Explanations), La Roche."},{"key":"ref_37","unstructured":"James, N.M., and Jane, C.M. (2005). Statistics and Chemometrics for Analytical Chemistry, Pearson Education Limited."},{"key":"ref_38","unstructured":"AstraZeneca Pharmaceuticals, L.P. (2026, July 01). Datasheet Meropenem (Merren TM) for Injection Powder for Inyectable, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2016\/050706s037lbl.pdf."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/chromsci\/48.5.406","article-title":"HPLC Method for Measuring Meropenem and Biapenem Concentrations in Human Peritoneal Fluid and Bile: Application to Comparative Pharmacokinetic Investigations","volume":"48","author":"Kameda","year":"2010","journal-title":"J. Chromatogr. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/S0731-7085(03)00366-2","article-title":"Validation of HPLC and UV spectrophotometric methods for the determination of meropenem in pharmaceutical dosage form","volume":"33","author":"Mendez","year":"2003","journal-title":"J. Pharm. BioMed. Anal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e3880","DOI":"10.1002\/bmc.3880","article-title":"Determination of meropenem levels in human serum by high-performance liquid chromatography with ultraviolet detection: Determination of meropenem in human serum","volume":"31","author":"Roth","year":"2017","journal-title":"BioMed. Chromatogr."},{"key":"ref_42","unstructured":"(2026, May 30). Monographie-Meropenem-Stabilis 4.0. Available online: https:\/\/www.stabilis.org\/Monographie.php?IdMolecule=340."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/ajhp\/54.4.412","article-title":"Stability of meropenem in intravenous solutions","volume":"54","author":"Patel","year":"1997","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_44","unstructured":"(2026, April 05). Stabilis 4.0. Level of Evidence of the Bibliographic References. Available online: https:\/\/www.stabilis.org\/voirFichierPDF.php?IdFichier=10793."},{"key":"ref_45","first-page":"283","article-title":"Stability of generic brands of meropenem reconstituted in isotonic saline","volume":"81","author":"Carlier","year":"2015","journal-title":"Minerva Anestesiol."},{"key":"ref_46","first-page":"357","article-title":"Stability Studies of Antipyocyanic Beta-Lactam Antibiotics Used in Continuous Infusion","volume":"74","author":"Curti","year":"2019","journal-title":"Pharm. Govi Verl. GMBH"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Loeuille, G., D\u2019Huart, E., Vigneron, J., Nisse, Y.-E., Beiler, B., Polo, C., Ayari, G., Sacrez, M., Demor\u00e9, B., and Charmillon, A. (2022). Stability Studies of 16 Antibiotics for Continuous Infusion in Intensive Care Units and for Performing Outpatient Parenteral Antimicrobial Therapy. Antibiotics, 11.","DOI":"10.3390\/antibiotics11040458"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.jtos.2017.05.002","article-title":"TFOS DEWS II pain and sensation report","volume":"15","author":"Belmonte","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1167\/iovs.16-19435","article-title":"Corneal Sensitivity to Hyperosmolar Eye Drops: A Novel Behavioral Assay to Assess Diabetic Peripheral Neuropathy","volume":"57","author":"Yorek","year":"2016","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.ajo.2010.10.032","article-title":"Tear osmolarity in the diagnosis and management of dry eye disease","volume":"151","author":"Lemp","year":"2011","journal-title":"Am. J. Ophthalmol."},{"key":"ref_52","unstructured":"Pharmacy Department, and Hospital General Universitario Gregorio Mara\u00f1\u00f3n (2021). Vancomycin 50 Mgml Eye Drops, Hospital General Universitario Gregorio Mara\u00f1\u00f3n. Available online: https:\/\/www.comunidad.madrid\/hospital\/gregoriomaranon\/sites\/gregoriomaranon\/files\/2022-02\/Vancomicina%2050%20mgml%20colirio.pdf."},{"key":"ref_53","unstructured":"Pharmacy Compounding Group, and Spanish Society of Hospital Pharmacy (2016). Vancomycin 50 mg\/mL Eye Drops 10 mL, Spanish Society of Hospital Pharmacy. Available online: https:\/\/gruposdetrabajo.sefh.es\/farmacotecnia\/images\/stories\/PN_Formulas\/V\/INF_VANCOMICINA_50_MG_enero2016.pdf."},{"key":"ref_54","unstructured":"Pharmacy Compounding Group, and Spanish Society of Hospital Pharmacy (2016). Ceftazidime 50 mg\/mL Eye Drops 10 mL, Spanish Society of Hospital Pharmacy. Available online: https:\/\/gruposdetrabajo.sefh.es\/farmacotecnia\/images\/stories\/PN_Formulas\/C\/INF_CEFTAZIDIMA_COLIRIO_50_MG_enero2016.pdf."},{"key":"ref_55","unstructured":"Pharmacy Department, and Hospital General Universitario Gregorio Mara\u00f1\u00f3n (2021). Ceftazidime 50 mgml Eye Drops, Hospital General Universitario Gregorio Mara\u00f1\u00f3n. Available online: https:\/\/www.comunidad.madrid\/hospital\/gregoriomaranon\/sites\/gregoriomaranon\/files\/2022-01\/Ceftazidima%2050%20mgml%20colirio.pdf."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/8\/971\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T13:21:33Z","timestamp":1786108893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/8\/971"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":55,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["pharmaceutics18080971"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18080971","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]}}}