{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T21:49:44Z","timestamp":1782337784561,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study presents a novel analytical and formulation strategy to enhance the oral delivery and quality assessment of Nirmatrelvir, a poorly water\u2010soluble antiviral agent. A self\u2010emulsifying drug delivery system (SEDDS) was developed using Labrafac MC 60, ethanol, and Transcutol HP (55:25:20), resulting in a nanoemulsion with a droplet size of 145.23\u2009\u00b1\u20093.23\u2009nm, low polydispersity index (0.189\u2009\u00b1\u20090.023), and high transmittance (98.97\u2009\u00b1\u20090.25%). The formulation exhibited rapid emulsification (&lt;\u200990\u2009s) and significantly improved permeability, achieving a fivefold increase (Papp: 4.20\u2009\u00d7\u200910\n                    <jats:sup>\u22126<\/jats:sup>\n                    \u2009cm\/s) across Caco\u20102 cell monolayers compared to the tablet formulation. A stability\u2010indicating reverse\u2010phase HPLC method was developed using a mobile phase of 5\u2009mM potassium dihydrogen phosphate buffer (pH 4.0) and acetonitrile (40:60, v\/v), and validated per ICH Q2(R1) guidelines. The method showed excellent linearity (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.9999), accuracy (98.6%\u2013100.2%), precision (%RSD\u2009&lt;\u20090.3%), and robustness. An optimized sample preparation protocol ensured efficient extraction of Nirmatrelvir from the SEDDS matrix with minimal interference. Forced degradation studies under ICH Q1A(R2) demonstrated that Nirmatrelvir remained stable under oxidative (98.44%), thermal (98.45%), and photolytic (98.50%) conditions. Maximum degradation was observed under alkaline stress (20.56% at 0.5\u2009N NaOH), followed by acidic stress (13.53% at 5\u2009N HCl). The major alkaline degradant (Rt 2.7\u2009min) was characterized by LC\u2010TQ\/MS (\n                    <jats:italic>m\/z<\/jats:italic>\n                    518.2 [M+H]\u207a). The method's sustainability was supported by an AGREE score of 0.64 and a Whiteness score of 85.4, offering a validated platform for routine analysis of Nirmatrelvir in lipid\u2010based formulations.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70100","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T06:48:36Z","timestamp":1758610116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Validated Stability\u2010Indicating RP\u2010HPLC Method for Nirmatrelvir in Self\u2010Emulsifying Drug Delivery Systems: Formulation Characterization and Permeability Enhancement"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7453-0122","authenticated-orcid":false,"given":"Ravi","family":"Patel","sequence":"first","affiliation":[{"name":"School of Pharmacy Gujarat Technological University Gandhinagar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritu","family":"Sharma","sequence":"additional","affiliation":[{"name":"School of Pharmacy Gujarat Technological University Gandhinagar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8850-7468","authenticated-orcid":false,"given":"Dignesh","family":"Khunt","sequence":"additional","affiliation":[{"name":"School of Pharmacy Gujarat Technological University Gandhinagar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4633-0411","authenticated-orcid":false,"given":"Binit","family":"Patel","sequence":"additional","affiliation":[{"name":"Hovione East Windsor New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2022.106708"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27175606"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2023.109707"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm3006433"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(96)00490-5"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408347.2024.2384046"},{"key":"e_1_2_8_8_1","volume-title":"Q3A (R2): Impurities in New Drug Substances","author":"ICH","year":"2006"},{"key":"e_1_2_8_9_1","volume-title":"Q2 (R2): Validation of Analytical 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