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Preliminary screening trials along with systemic risk analysis were performed, endeavouring to explicate the critical method attributes, namely pH, percentage orthophosphoric acid content and percentage methanol content, that influence critical quality attributes. Box\u2013Behnken design was utilized for the optimization of the tailing factor as response for methotrexate and mangiferin in short run time. The chromatographic conditions were optimized by performing 17 experimental runs acquired from Design\u2010Expert software. The chromatographic conditions after the analysis of an optimized zone within the confines of the design space were chosen as mobile phase water\u2013methanol adjusted to pH\u00a03.0 with 0.05% orthophosphoric acid (65:35, v\/v) and flow rate 1.0\u00a0ml\/min using a C<jats:sub>18<\/jats:sub> analytical column at an isosbestic wavelength of 265\u2009nm. Furthermore, the validation of the optimized method was done in accordance with International Conference on Harmonization guidelines and were reckoned to be in the prescribed limits. The developed RP\u2010HPLC method has a high degree of practical utility for synchronous detection of methotrexate and mangiferin in pharmaceutical nano\u2010dosage forms such as protein\u2010based\u2010nanoparticles, nanocrystals, polymeric nanoparticles and metallic nanoparticles in <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> studies.<\/jats:p>","DOI":"10.1002\/bmc.5648","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T05:10:55Z","timestamp":1681362655000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Application of a Quality by Design\u2010based approach in development and validation of an RP\u2010HPLC method for simultaneous estimation of methotrexate and mangiferin in dual drug\u2010loaded liposomes"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7857-1124","authenticated-orcid":false,"given":"Syeda Nashvia","family":"Adin","sequence":"first","affiliation":[{"name":"Phytomedicine Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research Jamia Hamdard  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-2967","authenticated-orcid":false,"given":"Isha","family":"Gupta","sequence":"additional","affiliation":[{"name":"Phytomedicine Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research Jamia Hamdard  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohd.","family":"Aqil","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Education and Research Jamia Hamdard  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7204-780X","authenticated-orcid":false,"given":"Mohd.","family":"Mujeeb","sequence":"additional","affiliation":[{"name":"Phytomedicine Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research Jamia Hamdard  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abul Kalam","family":"Najmi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Education and Research Jamia Hamdard  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,5,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.14978"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/pm.pm_160_22"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00764-022-00182-4"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5581"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2023.104209"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.5530\/097484900279"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2023.2173338"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.7897\/2230-8407.09689"},{"key":"e_1_2_8_10_1","first-page":"307","article-title":"Evaluation of antibacterial activity of Mangifera indica on anaerobic dental microglora based on in vivo studies","volume":"45","author":"Bairy I.","year":"2002","journal-title":"Indian Journal of Pathology & Microbiology"},{"key":"e_1_2_8_11_1","first-page":"168","article-title":"An improved LC\u2010MS\/MS method for the determination of mangiferin in rat plasma and its application in nonlinear pharmacokinetics","volume":"69","author":"Cai F.","year":"2014","journal-title":"Die Pharmazie\u2010An International Journal of Pharmaceutical Sciences"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.596"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2012.01.015"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.9529"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000239478"},{"key":"e_1_2_8_16_1","unstructured":"Guideline IHT. 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