{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T01:42:10Z","timestamp":1780710130782,"version":"3.54.1"},"update-to":[{"DOI":"10.12688\/f1000research.159438.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000}}],"reference-count":46,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    Background Diabetes mellitus type II is expected to impact a large population worldwide. Among the available therapeutic options, Metformin hydrochloride is a key medication, particularly for those who cannot effectively manage the condition through changes in diet and lifestyle alone. This research aimed to predict their\n                    <ns3:italic>in vivo<\/ns3:italic>\n                    parameters from an\n                    <ns3:italic>in vitro<\/ns3:italic>\n                    release study by developing a physiologically based pharmacokinetic (PBPK) model by using Gastroplus\n                    <ns3:sup>\u00ae<\/ns3:sup>\n                    software. Methods Sodium alginate-based MH floating beads were prepared by dissolving different concentrations of sodium alginate in deionized water, incorporating MH (1 g) and calcium carbonate (1.5 mg) as a gas-forming agent, and mixing at 200 rpm. The air-free dispersion, achieved through 30 minutes of sonication, was dropped into a 5% w\/v calcium chloride solution containing 5% v\/v isopropyl alcohol via a syringe for cross-linking and bead formation. Beads were cured in the solution for 30 minutes to enhance mechanical strength, then filtered, washed, and air-dried for 24 hours, ensuring uniformity and stability for controlled drug delivery and the prepared beads were evaluated for their entrapment efficiency %, morphology, floating property and\n                    <ns3:italic>in vitro<\/ns3:italic>\n                    release Ultimately, using Gastroplus\n                    <ns3:sup>\u00ae<\/ns3:sup>\n                    software, to predict the pharmacokinetic profile of\n                    <ns3:italic>in vitro<\/ns3:italic>\n                    release results. Results Entrapment efficiency exhibited acceptable values, and the beads were smooth, and rounded in shape for all formulations. The beads remained afloat during the release study; the release study revealed that F1 to F5 showed asymptotic slow-release, while F6 and F7 gave shorter release times. The prediction of absorption indicated highest MH absorption was in the jejunum, then the duodenum. Conclusion The prepared Beads had promising pharmacokinetic parameters and C max was close to MH modified released tablet.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.159438.2","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T12:15:16Z","timestamp":1757420116000},"page":"140","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Forecasting in vivo pharmacokinetics of metformin HCl floating beads using Gastroplus\u00ae PBPK"],"prefix":"10.12688","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0007-8441","authenticated-orcid":false,"given":"Sura Zuhair","family":"Mahmood","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6025-506X","authenticated-orcid":false,"given":"Nora Zawar","family":"Yousif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9601-4180","authenticated-orcid":false,"given":"Masar Basim","family":"Mohsin Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e2004","DOI":"10.1002\/hsr2.2004","article-title":"Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused.","volume":"7","author":"M Hossain","year":"2024","journal-title":"Health Sci. 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The author describes the methodology appropriately and well written in the manuscript. However, the references are not up-to-date and most of the cited references are before 2020.&nbsp;Moreover, the objective of this study was to develop floating beads which seems to be very old method and various studies have been already published for the same objective to formulate floating beads.&nbsp;  \n<b>Thank you for your valuable comments and observations. We have updated most of the references to ensure they are more current. While we acknowledge that the method used is established and considered an old technique, we believe it remains highly reproducible and capable of yielding reliable results. Furthermore, previous studies have not addressed the prediction of in vivo pharmacokinetics based on in vitro release data using this specific approach, which we believe adds novelty to our work, and this was referred to in the introduction section &nbsp;<\/b>  One of the paper is as follows: Nayak, A., Jain, S. K., &amp; Pandey, R. S. (2011 [Ref-1]). Controlling release of metformin HCl through incorporation into stomach specific floating alginate beads.&nbsp;\n<i>Molecular pharmaceutics<\/i>,&nbsp;\n<i>8<\/i>(6), 2273-2281. \n<b>Kindly refer to the introduction and reference sections, which were changed to more recent ones as per your request<\/b>\n<b> <\/b>  The interpretation of results should be discussed in depth to explain the possible reasons behind the results&nbsp; \n<b>Thank you for pointing this out. The revised version now includes a more detailed explanation<\/b>\n<b> and is highlighted within the result section. <\/b>","URL":"https:\/\/f1000research.com\/articles\/14-140\/v2#referee-comment-14091","order":2,"name":"referee-comment-14091","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.183289.r414010, Sadia Rehman, Murryam Nawaz, Riphah International University, Islamabad, 30 Sep 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/14-140\/v2#referee-response-414010","order":3,"name":"referee-response-414010","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}