{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T09:05:20Z","timestamp":1771232720583,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Drug\u2013food interactions may compromise therapeutic efficacy, particularly for life\u2010saving medications such as anticoagulants. Changes in gastric fluid properties, including pH modification and surface film formation, can alter drug dissolution and release. This study evaluated a potential interaction between clopidogrel and spinach and explored the underlying mechanisms. In\u00a0vitro disintegration and dissolution studies were conducted using HCl and phosphate buffers with and without 5% and 7.5% spinach extract. Drug release was quantified by high\u2010performance liquid chromatography (HPLC), with six media conditions analyzed in triplicate. Disintegration testing was performed in simulated gastric and intestinal fluids and in the presence of spinach leaves to assess the effect of film formation on tablet wetting and disintegration. In\u00a0vitro\u2013in vivo extrapolation (IVIVE) was assessed using GastroPlus software. Clopidogrel dissolution decreased with increasing spinach concentration in both media. In HCl buffer, dissolution declined from 99% to 94% and 89%, while in phosphate buffer it decreased from 71% to 66% and 56%. These effects were associated with increased pH (HCl: 1.91, 2.83, 2.98; phosphate: 6.81, 8.83, 6.84), increased solution viscosity, 17.63 to 17.67 and 17.70 in HCl buffer, and from 17.44 to 17.50 and 17.54 in phosphate buffer. Moreover, reduced fluid penetration was due to spinach leaves coverage. IVIVE analysis showed weak correlations (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.74 in HCl and 0.69 in phosphate buffer). Spinach reduced clopidogrel dissolution in\u00a0vitro, with statistically significant effects at 5% spinach in HCl buffer (ANOVA test,\n                    <jats:italic>p<\/jats:italic>\n                    \u2010value 0.019) and 7.5% in phosphate buffer (ANOVA test,\n                    <jats:italic>p<\/jats:italic>\n                    \u2010value &lt;\u20090.001). This interaction appears to be mediated by pH alteration, physical film formation, and potentially metal\u2013drug complexation. Confirmation through in\u00a0vivo studies is warranted.\n                  <\/jats:p>","DOI":"10.1002\/prp2.70223","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T13:51:32Z","timestamp":1770990692000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of\n                    <scp>\n                      <i>Spinacia oleracea<\/i>\n                    <\/scp>\n                    on In\u00a0Vitro Disintegration and Dissolution of Clopidogrel Bisulfate Tablets"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0317-4818","authenticated-orcid":false,"given":"Dana","family":"Sadaqa","sequence":"first","affiliation":[{"name":"Pharmacy Department, Faculty of Pharmacy, Nursing and Health Professions Birzeit University  Birzeit Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9700-8532","authenticated-orcid":false,"given":"Hani A.","family":"Naseef","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Faculty of Pharmacy, Nursing and Health Professions Birzeit University  Birzeit Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5531-0805","authenticated-orcid":false,"given":"Asma","family":"Radwan","sequence":"additional","affiliation":[{"name":"College of Pharmacy An\u2010Najah National University  Nablus Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5323-712X","authenticated-orcid":false,"given":"Abdullah K.","family":"Rabba","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Faculty of Pharmacy, Nursing and Health Professions Birzeit University  Birzeit Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramzi H. M.","family":"Muqedi","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Faculty of Pharmacy, Nursing and Health Professions Birzeit University  Birzeit Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/S40780\u2010019\u20100155\u20101"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01061694"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.7324\/JAPS.2024.160197"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/CLPT.2013.192"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.ARABJC.2014.08.001"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/DMD.31.1.53"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.EJPS.2017.01.030"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CCR.2016.04.009"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6FO00051G"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/IJERPH14030301"},{"key":"e_1_2_13_12_1","first-page":"160","volume-title":"Antiplatelet Therapy in Cardiovascular Disease","author":"Beavers C. 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