{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T10:38:21Z","timestamp":1777718301511,"version":"3.51.4"},"reference-count":14,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Zydus Lifesciences Limited, Ahmedabad, India"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Toxicol"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>These toxicity studies aimed to assess the safety and tolerability of a novel intravenous diclofenac sodium (37.5\u00a0mg\/mL) formulation containing povidone K12 (80\u00a0mg\/mL) as the key excipient in Wistar rats. This formulation was tested at doses of 3, 7, and 15\u00a0mg\/kg\/day and was administered daily for 28 days by intravenous route. Toxicokinetic estimation revealed a dose-proportional increase in plasma exposure to diclofenac. The formulation was well tolerated in males; however, mortality was observed in females (2\/15) at the highest dose (15\u00a0mg\/kg\/day). Adverse gastrointestinal events related to NSAIDS and a few other treatment-related effects on clinical and anatomic pathology were noted at the 15\u00a0mg\/kg\/day dose, which normalized at the end of the 2-week recovery period. In addition, the excipient povidone K12 was present in a higher amount than the approved Inactive Ingredient Database (IID) limit in the proposed novel formulation. It was qualified through a separate 28-day repeated dose toxicity study by intravenous route in Wistar rats. Povidone K12 was found to be well tolerated and safe up to a dose of 165\u00a0mg\/kg\/day. No treatment-related adverse effects were observed in this study. In conclusion, repeated administration of a novel intravenous formulation containing diclofenac sodium was found to be safe up to the dose of 7\u00a0mg\/kg\/day in female rats and 15\u00a0mg\/kg\/day in male rats.<\/jats:p>","DOI":"10.1177\/10915818241261922","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T19:39:38Z","timestamp":1718912378000},"page":"491-502","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety Assessment of a Novel Intravenous Diclofenac Sodium Formulation Following 28-Day Repeated Administration in Wistar Rats"],"prefix":"10.1177","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1227-7408","authenticated-orcid":false,"given":"Laxit K.","family":"Bhatt","sequence":"first","affiliation":[{"name":"Department of Pharmacology & Toxicology, Zydus Research Centre, Zydus Lifesciences Limited, Ahmedabad, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chitrang R.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Zydus Research Centre, Zydus Lifesciences Limited, Ahmedabad, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jitendra H.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Zydus Research Centre, Zydus Lifesciences Limited, Ahmedabad, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viral I.","family":"Rajwadi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Zydus Research Centre, Zydus Lifesciences Limited, Ahmedabad, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pankaj","family":"Dwivedi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Zydus Research Centre, Zydus Lifesciences Limited, Ahmedabad, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajesh J.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Zydus Research Centre, Zydus Lifesciences Limited, Ahmedabad, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramchandra K.","family":"Ranvir","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Zydus Research Centre, Zydus Lifesciences Limited, Ahmedabad, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harilal","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Zydus Research Centre, Zydus Lifesciences Limited, Ahmedabad, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajesh","family":"Sundar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Zydus Research Centre, Zydus Lifesciences Limited, Ahmedabad, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mukul R.","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Zydus Research Centre, Zydus Lifesciences Limited, Ahmedabad, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,6,20]]},"reference":[{"key":"bibr1-10915818241261922","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200868010-00008"},{"key":"bibr2-10915818241261922","volume-title":"Diclofenac","author":"Alfaro RA","year":"2024"},{"key":"bibr3-10915818241261922","volume-title":"Gahart\u2019s 2018 Intravenous Medications: A Handbook for Nurses and Other Allied Health Personnel","author":"Gahart BL","year":"2017"},{"key":"bibr4-10915818241261922","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0392-z"},{"key":"bibr5-10915818241261922","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2005.03.007"},{"key":"bibr6-10915818241261922","unstructured":"Dyloject (Diclofenac sodium) injection. 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