{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:18:39Z","timestamp":1788877119004,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Administration of oral medicinal products as crushed tablets or open capsules is an important delivery option for patients suffering from dysphagia. To obtain full interchangeability of generics with the original products, demonstration of bioequivalence (BE) between both products administered as crushed tablets\/open capsules was required for poorly soluble product by European Medicines Agency (EMA) at the time of development of our rivaroxaban and deferasirox generic products. We present the results of two BE studies with modified administration of these products, which compared relative bioavailability between generic and reference products. In the rivaroxaban study, the test product was administered as a capsule sprinkled on and mixed with applesauce, whereas the reference tablet was crushed and administered with applesauce under fed conditions. In the deferasirox study, both treatments were administered as crushed tablets under fasting conditions. Both studies applied a two\u2010way crossover design and were conducted after a single\u2010dose in healthy volunteers. The 90% confidence interval of the geometric mean ratio area under the analyte concentration versus time curve, from time zero to the time of the last measurable analyte concentration and maximum measured analyte concentration over the sampling period of the test to reference ratio were 103.36\u2013110.37% and 97.98\u2013108.45% for rivaroxaban, respectively, and 96.69\u2013107.29% and 94.19\u2013109.45% for deferasirox, respectively. Thus, the BE criteria (80.00\u2013125.00%) were met in both studies which demonstrated that bioavailability was not affected when the test and reference products were administered in the form of crushed tablet\/open capsule. These results support the argument of redundancy of crushed product studies for poorly soluble drugs, which is in line with the currently revised position of the EMA on this topic.<\/jats:p>","DOI":"10.1111\/cts.13752","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T10:15:50Z","timestamp":1711016150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Crushing tablets or sprinkling capsules: Implications for clinical strategy and study performance based on <scp>BE<\/scp> studies of rivaroxaban and deferasirox"],"prefix":"10.1111","volume":"17","author":[{"given":"Jan","family":"Sus","sequence":"first","affiliation":[{"name":"Zentiva, k.s.  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Bosak","sequence":"additional","affiliation":[{"name":"Zentiva, k.s.  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Hauser","sequence":"additional","affiliation":[{"name":"Zentiva, k.s.  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11092605"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12467"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00455-015-9671-9"},{"issue":"4","key":"e_1_2_9_5_1","first-page":"180","article-title":"Prevalence of dysphagia in multiple sclerosis and its related factors: systematic review and meta\u2010analysis","volume":"17","author":"Aghaz A","year":"2018","journal-title":"Iran J Neurol"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12030863"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03380-0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2007.11.063"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00455-016-9707-9"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.6061\/clinics\/2020\/e1556"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.02.045"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S6529"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.5009\/gnl15502"},{"issue":"1","key":"e_1_2_9_14_1","first-page":"25","article-title":"Efficacy of a new microencapsulated pancreatin versus a conventional preparation, in the treatment of steatorrhea of pancreatic origin","volume":"76","author":"Aparisi L","year":"1989","journal-title":"Rev Esp Enferm Apar Dig"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198510040-00001"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2020.11817"},{"issue":"12","key":"e_1_2_9_17_1","first-page":"1152","article-title":"Alendronate\u2010associated esophageal injury: pathologic and endoscopic features","volume":"12","author":"Abraham SC","year":"1999","journal-title":"Mod Pathol"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0003489420906187"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00894-013-1780-5"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1011-1344(98)00111-0"},{"key":"e_1_2_9_21_1","volume-title":"Summary of Product Characteristics, Xarelto 20 mg film\u2010coated tablets","year":"2009"},{"key":"e_1_2_9_22_1","volume-title":"Summary of product characteristics, Exjade 360 mg, film\u2010coated tablets","year":"2009"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0100-7"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2016.05.004"},{"key":"e_1_2_9_25_1","volume-title":"Clinical pharmacology and pharmacokinetics: questions and answers","author":"European Medicines Agency","year":"2019"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13752","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T06:32:54Z","timestamp":1744871574000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/cts.13752"],"URL":"https:\/\/doi.org\/10.1111\/cts.13752","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"2023-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13752"}}