{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T21:54:47Z","timestamp":1781560487132,"version":"3.54.5"},"reference-count":23,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2023,11,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>This article aims to describe a preclinical proof of concept for a novel once-a-day (OD) brimonidine ophthalmic nanosuspension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>The preclinical proof of concept was established using New Zealand white rabbits as animal models. Dose-finding, multiple-dose efficacy, ocular pharmacokinetic, and hemodynamic studies were performed in normotensive rabbits. Steroid-induced ocular hypertension model in rabbits was used to study efficacy in glaucomatous pathophysiology. The test (0.35% OD suspension) and reference (0.15% three times a day [TID] solution) were compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The intraocular pressure (IOP) reduction was sustained for 0.35% and 0.5% strengths but not for other lower strengths tested or reference strengths. A 0.35% OD suspension reduced IOP &gt;2\u2009mmHg after 24\u2009h of dosing, which was not seen with the reference. After multiple dosing, 0.35% OD suspension reduced IOP by 4\u20136\u2009mmHg after 24\u2009h, which was comparable to the 0.15% TID reference solution. An ocular pharmacokinetic study showed that the brimonidine was rapidly absorbed and distributed throughout the eye after topical administration. Concentration was higher in tissues with high \u03b1\n                      <jats:sub>2<\/jats:sub>\n                      receptors, such as cornea\u2013conjunctiva, iris\/ciliary body, and choroid\/retina. The steady-state concentrations in these organs were also significant after 24\u2009h of the last dose. There was an indication of increased plasma levels, so a hemodynamic study was performed to assess any adverse effects. All hemodynamic parameters were normal and no new unusual safety findings were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The study demonstrated that the novel brimonidine 0.35% ophthalmic nanosuspension is both safe and effective when administered OD and is comparable to the marketed reference formulation administered TID.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2023.0038","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T10:34:16Z","timestamp":1693391656000},"page":"631-642","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Preclinical Evaluation of a Novel Once-a-Day Brimonidine Ophthalmic Nanosuspension"],"prefix":"10.1177","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3519-7731","authenticated-orcid":false,"given":"Ajay J.","family":"Khopade","sequence":"first","affiliation":[{"name":"Department of Formulation R&amp;D Non-Orals, Sun Pharmaceutical Industries Ltd., Vadodara, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arindam","family":"Halder","sequence":"additional","affiliation":[{"name":"Department of Formulation R&amp;D Non-Orals, Sun Pharmaceutical Industries Ltd., Vadodara, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Formulation R&amp;D Non-Orals, Sun Pharmaceutical Industries Ltd., Vadodara, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivam","family":"Upadhyay","sequence":"additional","affiliation":[{"name":"Department of Formulation R&amp;D Non-Orals, Sun Pharmaceutical Industries Ltd., Vadodara, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Burade","sequence":"additional","affiliation":[{"name":"Department of Formulation R&amp;D Non-Orals, Sun Pharmaceutical Industries Ltd., Vadodara, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Pateliya","sequence":"additional","affiliation":[{"name":"Department of Formulation R&amp;D Non-Orals, Sun Pharmaceutical Industries Ltd., Vadodara, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Panchal","sequence":"additional","affiliation":[{"name":"Department of Translational Development, Sun Pharma Advanced Research Company Ltd., Vadodara, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Mandhane","sequence":"additional","affiliation":[{"name":"Department of Translational Development, Sun Pharma Advanced Research Company Ltd., Vadodara, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandan","family":"Awati","sequence":"additional","affiliation":[{"name":"Department of Formulation R&amp;D Non-Orals, Sun Pharmaceutical Industries Ltd., Vadodara, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murlidhar","family":"Zope","sequence":"additional","affiliation":[{"name":"Department of Formulation R&amp;D Non-Orals, Sun Pharmaceutical Industries Ltd., Vadodara, India."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3192"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804630"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.120.6.701"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1995.01100120044006"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.2147\/tcrm.2006.2.4.337"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.4103\/0253-7613.44151"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.2165\/00002512-200825090-00002"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00061198-200310000-00001"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/IJG.0b013e3181f3eb4a"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.2010.02050.x"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2022.103594"},{"key":"e_1_3_8_13_2","unstructured":"U.S. Food and Drug Administration. 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