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  <front>
    <journal-meta>
      <journal-id journal-id-type="iso-abbrev">Pharmacophore</journal-id>
      <journal-id journal-id-type="publisher-id">pharmacophorejournal.com</journal-id>
      <journal-id journal-id-type="publisher-id">Pharmacophore</journal-id>
      <journal-title-group>
        <journal-title>Pharmacophore</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2229-5402</issn>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">pharmacophorejournal.com-6979</article-id>
      <article-id pub-id-type="doi">10.51847/HXSioqastj</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original research</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>When Does a Pharmaceutical Model Become a Digital Twin? An Umbrella Review across Pharmacology, Pharmaceutics, and Drug Delivery</article-title>
      </title-group>
                    <contrib-group>
                      <contrib contrib-type="author">
              <name>
                <surname>Nkosi</surname>
                <given-names>Thabo</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                                            <xref rid="cor1" ref-type="corresp" />
                          </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Molefe</surname>
                <given-names>Lerato</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Dlamini</surname>
                <given-names>Sipho</given-names>
              </name>
                              <xref rid="aff2" ref-type="aff">2</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Mokoena</surname>
                <given-names>Ayanda</given-names>
              </name>
                              <xref rid="aff3" ref-type="aff">3</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Ndlovu</surname>
                <given-names>Kabelo</given-names>
              </name>
                              <xref rid="aff4" ref-type="aff">4</xref>
                                        </contrib>
                  </contrib-group>
                  <aff id="aff1">
            <label>1</label>Department of Digital Twin Definition and Umbrella Review, Faculty of Pharmacy, University of Cape Town, Cape Town, South Africa.
          </aff>
                  <aff id="aff2">
            <label>2</label>Department of Pharmaceutical Digital Twins in Drug Delivery, Faculty of Pharmacy, University of the Witwatersrand, Johannesburg, South Africa.
          </aff>
                  <aff id="aff3">
            <label>3</label>Department of Pharmacology and Pharmaceutics Twins, Faculty of Pharmaceutical Sciences, University of Pretoria, Pretoria, South Africa.
          </aff>
                  <aff id="aff4">
            <label>4</label>Department of Model-to-Twin Translation, Faculty of Pharmacy, Stellenbosch University, Stellenbosch, South Africa.
          </aff>
                          <author-notes>
            <corresp id="cor1">
              <bold>Address for correspondence:</bold> Prof. Wael Abu Dayyih, Department of
              Pharmaceutical Chemistry, Faculty of Pharmacy, Mutah University, Al-Karak 61710, Jordan.
                              E-mail: <email xlink:href="thabo.nkosi@uct.ac.za">thabo.nkosi@uct.ac.za</email>
                          </corresp>
          </author-notes>
                    <pub-date pub-type="epub">
        <day>28</day>
        <month>08</month>
        <year>2026</year>
      </pub-date>
      <volume>17</volume>
      <issue>4</issue>
      <fpage>135</fpage>
      <lpage>145</lpage>
      <permissions>
        <copyright-statement>
          Copyright: &#x000a9; 2026 Pharmacophore
        </copyright-statement>
        <copyright-year>2026</copyright-year>
        <license>
          <ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/"
            specific-use="textmining" content-type="ccbyncsalicense">
            https://creativecommons.org/licenses/by-nc-sa/4.0/</ali:license_ref>
          <license-p>This is an open access journal, and articles are distributed under the terms of
            the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows
            others to remix, tweak, and build upon the work non-commercially, as long as appropriate
            credit is given and the new creations are licensed under the identical terms.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>A<sc>BSTRACT</sc></title>
        <p>Digital-twin terminology is increasingly applied to computational models used in drug discovery, pharmacology, formulation development, drug delivery, precision dosing, clinical trials, and pharmaceutical manufacturing. However, patient-specific simulation, mechanistic modeling, adaptive prediction, virtual populations, and process monitoring are frequently described as digital twins without consistent requirements for real-entity linkage, updating, uncertainty assessment, or decision use. This umbrella review critically evaluates review-level evidence across pharmaceutical domains to determine when a model warrants the digital-twin designation. The synthesis distinguishes digital models, adaptive models, virtual patients, digital shadows, and decision-coupled twins according to counterpart identity, data connection, update logic, predictive purpose, bidirectional information flow, validation, and governance. Review selection, methodological quality, primary-study overlap, consistency, and context of use are treated as determinants of evidentiary strength rather than assuming that multiple reviews constitute independent confirmation. The evidence indicates that pharmacometric, systems-pharmacology, formulation, delivery, and manufacturing models provide important twin-enabling capabilities, but most reported applications demonstrate only subsets of the functions implied by a mature digital twin. Patient specificity, mechanistic sophistication, or benchmark performance alone does not establish twin status. The central contribution is a proposed operational boundary in which a pharmaceutical digital twin must represent a specified counterpart, receive state-relevant updates, generate uncertainty-aware prospective predictions, and connect those predictions to an auditable and bounded decision pathway. This framework is conceptual and requires domain-specific validation. Its purpose is not to promote universal adoption of digital twins, but to improve terminology, evidence appraisal, comparative evaluation, and translational judgment across computational pharmaceutical science.</p>
      </abstract>
      <kwd-group>
                <kwd>Digital twin</kwd>
                <kwd>Computational pharmacology</kwd>
                <kwd>Pharmaceutics</kwd>
                <kwd>Drug delivery modeling</kwd>
                <kwd>Virtual patients</kwd>
                <kwd>Model-informed precision dosing</kwd>
              </kwd-group>
    </article-meta>
  </front>
</article>