{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T13:04:04Z","timestamp":1784379844321,"version":"3.55.0"},"reference-count":14,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ibuprofen is the most commonly used NSAID; however, its short biological half\u2010life, reflected in the short duration of pain relief, limits the comfortableness of its usage. This study evaluated the pharmacokinetic properties of a newly developed biphasic ibuprofen 400\u2009mg immediate\u2010release\/sustained\u2010release (IR\/SR) modified\u2010release tablets (test formulation), which was developed with an aim to overcome a need for frequent dosing. Both single\u2010dose and multiple\u2010dose, open\u2010label, randomized, crossover studies compared the bioavailability of the test formulation with two Nurofen 200\u2009mg, immediate\u2010release coated tablets (reference formulation) administered within 4\u2009h intervals. In addition, the effect of food on the test formulation performance was evaluated in a single\u2010dose, open\u2010label, randomized, crossover, bioavailability study. Based on the 95% confidence intervals of the geometric mean ratios, the new test formulation exhibited equivalent (80.00\u2013125.00%) total (AUC\n                    <jats:sub>t,ss<\/jats:sub>\n                    ), peak (C\n                    <jats:sub>max,ss<\/jats:sub>\n                    ), and minimum (C\n                    <jats:sub>min,ss<\/jats:sub>\n                    ) steady\u2010state exposure compared to the reference product after repeated dosing. After a single dose of the test formulation, total (AUC\n                    <jats:sub>t<\/jats:sub>\n                    and AUC\n                    <jats:sub>\u221e<\/jats:sub>\n                    ) and peak (C\n                    <jats:sub>max0\u20104<\/jats:sub>\n                    ) exposure were bioequivalent to the reference. Food intake did not significantly alter the rate or extent of drug absorption from this product. The study medication was well\u2010tolerated. This ibuprofen test formulation may represent a potentially advantageous therapeutic alternative, providing extended relief of mild to moderate pain. While these considerations are supported by pharmacokinetic data, further clinical evaluation may help to better characterize their relevance in practice. The formulation may be particularly suitable for conditions where less frequent dosing is desirable, such as dental and back pain, or nighttime pain.\n                  <\/jats:p>","DOI":"10.1111\/cts.70654","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T03:33:16Z","timestamp":1782790396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of a Biphasic Modified\u2010Release Ibuprofen Tablet Formulation: Single\u2010Dose and Multiple\u2010Dose Pharmacokinetics and Food\u2010Effect Studies"],"prefix":"10.1111","volume":"19","author":[{"given":"Ludmila","family":"Kvapilov\u00e1","sequence":"first","affiliation":[{"name":"Zentiva, k.s  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u0159\u00ed","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Zentiva, k.s  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"\u010cern\u00fd","sequence":"additional","affiliation":[{"name":"Zentiva, k.s  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"Hauser","sequence":"additional","affiliation":[{"name":"Zentiva, k.s  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Bouhajib","sequence":"additional","affiliation":[{"name":"Pharma Medica Research, Inc.  Mississauga Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6541-738X","authenticated-orcid":false,"given":"Martin","family":"\u0160\u00edma","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, First Faculty of Medicine Charles University and General University Hospital  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ond\u0159ej","family":"Slana\u0159","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, First Faculty of Medicine Charles University and General University Hospital  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Summary of Product Characteristics. Nurofen 200 mg Tablets","author":"Reckitt Benckiser Healthcare (UK) Ltd","year":"2023"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.5001\/omj.2010.49"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199834020-00002"},{"key":"e_1_2_10_5_1","unstructured":"\u201cGuidance for Industry Bioanalytical Method Validation\u2010US Department of Health and Human Services Food and Drug Administration \u201d(2018)."},{"key":"e_1_2_10_6_1","unstructured":"\u201cGuideline on Bioanalytical Method Validation \u2010 European Medicines Agency EMEA\/CHMP\/EWP\/192217\/2009 \u201d(2025)."},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.288"},{"key":"e_1_2_10_8_1","volume-title":"Guideline on the Pharmacokinetic and Clinical Evaluation of Modified Release Dosage Forms (EMA\/CPMP\/EWP\/280\/96 Corr1)","author":"European Medicines Agency","year":"2014"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-014-0070-8"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270005279579"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470094778"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.12053"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010389470"},{"key":"e_1_2_10_14_1","unstructured":"European Medicine Agency \u201cIbuprofen Product\u2010Specific Bioequivalence Guidance. EMA\/CHMP\/356876\/2017 \u201d(2025)."},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/chir.22598"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70654","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70654","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70654","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T12:52:18Z","timestamp":1784379138000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70654"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":14,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/cts.70654"],"URL":"https:\/\/doi.org\/10.1111\/cts.70654","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]},"assertion":[{"value":"2026-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70654"}}