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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-6939</article-id>
      <article-id pub-id-type="doi">10.51847/m4IUvR5b3Z</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original research</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Designing the Depot Backward from a Target Exposure Profile for Long-Acting Injectable Medicines</article-title>
      </title-group>
                    <contrib-group>
                      <contrib contrib-type="author">
              <name>
                <surname>Kumar</surname>
                <given-names>Ravi</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                                            <xref rid="cor1" ref-type="corresp" />
                          </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Sharma</surname>
                <given-names>Neha</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Deshmukh</surname>
                <given-names>Aniket</given-names>
              </name>
                              <xref rid="aff2" ref-type="aff">2</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Kulkarni</surname>
                <given-names>Sanjay</given-names>
              </name>
                              <xref rid="aff3" ref-type="aff">3</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Nair</surname>
                <given-names>Arjun</given-names>
              </name>
                              <xref rid="aff4" ref-type="aff">4</xref>
                                        </contrib>
                  </contrib-group>
                  <aff id="aff1">
            <label>1</label>Department of Depot Design and Target Exposure Profiling, Faculty of Pharmacy, Indian Agricultural Research Institute, New Delhi, India.
          </aff>
                  <aff id="aff2">
            <label>2</label>Department of Long-Acting Injectable Formulation, Faculty of Pharmacy, IIT Bombay, Mumbai, India.
          </aff>
                  <aff id="aff3">
            <label>3</label>Department of Backward Design from Exposure Profile, Faculty of Pharmaceutical Sciences, Savitribai Phule Pune University, Pune, India.
          </aff>
                  <aff id="aff4">
            <label>4</label>Department of Long-Acting Medicine Development, Faculty of Pharmacy, IIT Kharagpur, Kharagpur, India.
          </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="ravi.kumar@iari.res.in">ravi.kumar@iari.res.in</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>93</fpage>
      <lpage>103</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>Long-acting injectable medicines are commonly developed by selecting a depot platform, adjusting formulation variables, and then evaluating the resulting release and pharmacokinetic behavior. This forward sequence can produce technically sophisticated formulations while leaving the governing therapeutic question incompletely specified: what depot behavior is required to generate an intended exposure trajectory across realistic patients, administration conditions, and manufacturing variation? This article develops Exposure-Constrained Depot Inverse Design, a proposed theory for designing the depot backward from a multidimensional target exposure specification. The approach decomposes the desired concentration–time behavior into admissible drug-input functions; maps those functions to molecular, material, formulation, administration, and process variables; represents depot formation, transformation, local tissue response, and systemic uptake as coupled dynamic processes; applies feasibility and manufacturability constraints before candidate acceptance; and requires forward evaluation across virtual populations and perturbation scenarios. The central contribution is a shift from maximizing a single output, such as nominal duration or cumulative release, toward identifying a robust feasibility envelope in which exposure requirements, depot physics, physiological variability, analytical observability, and product-development constraints remain simultaneously compatible. The theory distinguishes systemic exposure from in vivo input, intrinsic material behavior from the in vitro measurement system, and computational prioritization from experimental confirmation. Its principal limitations are non-uniqueness of the inverse problem, incomplete observability of depot states, model-form and parameter uncertainty, platform dependence, and limited human injection-site evidence. The proposed architecture may support more traceable formulation hypotheses and more informative validation studies, but it does not constitute a validated predictive model, clinical dosing framework, manufacturing control strategy, or regulatory decision tool.</p>
      </abstract>
      <kwd-group>
                <kwd>Long-acting injectables</kwd>
                <kwd>Depot drug delivery</kwd>
                <kwd>Inverse design</kwd>
                <kwd>Target exposure profile</kwd>
                <kwd>Mechanistic pharmacokinetics</kwd>
                <kwd>Release modeling</kwd>
              </kwd-group>
    </article-meta>
  </front>
</article>