{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:06:09Z","timestamp":1789027569494,"version":"build-2803163510"},"reference-count":62,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease requires innovative therapeutic strategies that not only alleviate symptoms but also protect neurons. Donepezil hydrochloride, a cholinesterase inhibitor, and quercetin, a potent antioxidant, were co\u2010formulated into a transethosomal gel to enhance brain delivery and therapeutic efficacy. To design and optimize a Quality by Design (QbD)\u2010based transethosomal gel containing Donepezil hydrochloride and Quercetin, and to establish a stability\u2010indicating, eco\u2010compatible RP\u2010HPLC method for their simultaneous estimation. Chromatographic separation was achieved on a C18 ODS column using an eco\u2010friendly mobile phase of acetonitrile\u2013phosphate buffer (45:55, pH 3.4). Detection was performed at 240\u2009nm, the isoabsorptive wavelength for both drugs. Method validation followed ICH guidelines, and forced degradation studies (acidic, basic, oxidative, thermal, photolytic) were conducted to achieve controlled degradation (5%\u201320%) while minimizing the use of hazardous solvents. The transethosomal gel was developed using QbD algorithms, optimizing critical parameters including particle size distribution (PDI), zeta potential, entrapment efficiency, and drug release profile. The optimized gel exhibited a vesicle size of 128.4\u2009\u00b1\u20092.1\u2009nm, PDI of 0.135, zeta potential of +29.52\u2009mV, and 89% and 85% entrapment efficiency of Quercetin and Donepezil HCl. Drug content exceeded 97% for both drugs, while cumulative drug release reached approximately 85%\u201395% over 10\u2009h. The RP\u2010HPLC method demonstrated excellent linearity (R\n                    <jats:sup>2<\/jats:sup>\n                    \u2009&gt;\u20090.995), recovery (98\u2212102%), precision (%RSD\u2009&lt;\u20092%), accuracy, robustness, and an Eco\u2010Scale score of 83.18, confirming excellent analytical greeness. Forced degradation studies confirmed its stability\u2010indicating capability. The study successfully integrates QbD\u2010driven formulation design with a validated eco\u2010friendly RP\u2010HPLC method, providing a robust platform for simultaneous drug delivery in Alzheimer's therapy. This work underscores the synergistic potential of advanced formulation strategies and sustainable analytical validation in translational pharmaceutical research.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70371","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:19:24Z","timestamp":1787566764000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quality by Design\u2010Guided Transethosomal Gel of Donepezil Hydrochloride and Quercetin for Potential Alzheimer's Management: Stability\u2010Indicating Eco\u2010Compatible RP\u2010HPLC Method"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4653-0233","authenticated-orcid":false,"given":"Abhishek","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis Laureate Institute of Pharmacy Kangra Himachal Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2330-2960","authenticated-orcid":false,"given":"Aditi","family":"Kaushik","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis Laureate Institute of Pharmacy Kangra Himachal Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arti","family":"Devi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis Laureate Institute of Pharmacy Kangra Himachal Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0775-9998","authenticated-orcid":false,"given":"Amar Deep","family":"Ankalgi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis Laureate Institute of Pharmacy Kangra Himachal Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7188-426X","authenticated-orcid":false,"given":"M. S.","family":"Ashawat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics Laureate Institute of Pharmacy Kangra Himachal Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8393-8931","authenticated-orcid":false,"given":"Hanan M.","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy Umm Al\u2010Qura University Makkah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5750-9886","authenticated-orcid":false,"given":"Manna","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy Umm Al\u2010Qura University Makkah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7441-1151","authenticated-orcid":false,"given":"Alaa A.","family":"Khojah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy Umm Al\u2010Qura University Makkah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3875-0235","authenticated-orcid":false,"given":"Shoeb","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Computational Biology Research Laboratory, Department of Pharmacy Daffodil International University Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5643-9202","authenticated-orcid":false,"given":"Magdi E. 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