{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:29:27Z","timestamp":1785403767752,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Social Fund\u2014the Human Capital Operational Programme","award":["POCU\/993\/6\/13\/154722"],"award-info":[{"award-number":["POCU\/993\/6\/13\/154722"]}]},{"award":["POCU\/993\/6\/13\/154722"],"award-info":[{"award-number":["POCU\/993\/6\/13\/154722"]}],"id":[{"id":"https:\/\/ror.org\/048snh465","id-type":"ROR","asserted-by":"publisher"}]},{"name":"University of Medicine and Pharmacy","award":["15\/.01.2021"],"award-info":[{"award-number":["15\/.01.2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Diclofenac (DCF) and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain and inflammation management; however, their clinical significance is limited by poor aqueous solubility, short biological half-life, and dose-dependent gastrointestinal, renal, and cardiovascular adverse effects. Nanocarrier-based delivery systems have been extensively explored because they can enhance the apparent solubility of poorly water-soluble NSAIDs, provide controlled and sustained drug release, prolong systemic circulation, and improve drug localization at the site of action. By reducing peak plasma concentrations and off-target exposure, these systems may decrease dose-dependent gastrointestinal and systemic adverse effects while maintaining therapeutic efficacy. Most studies focus on optimizing formulation composition, while the manufacturing process is often treated as a secondary parameter. The research critically evaluates conventional and emerging fabrication methods for NSAID nanocarriers, using DCF as the principal reference compound, with emphasis on their impact on physicochemical characteristics, reproducibility, scalability, and translational potential. Methods: A structured literature search was performed in PubMed\/MEDLINE, Scopus, and Web of Science (2015\u20132026, with emphasis on 2022\u20132026) for DCF and NSAID-loaded submicron delivery systems reporting quantitative formulation data and clearly defined fabrication methods, resulting in a narrative review of approximately 375\u2013395 eligible studies, comprising 75 DCF-specific studies and approximately 300\u2013320 studies involving other NSAIDs that were included as representative surrogate systems when DCF-specific evidence was unavailable for particular fabrication approaches. The review followed Scale for the Assessment of Narrative Review Articles (SANRA) recommendations. Studies were analyzed using a standardized seven-parameter framework including encapsulation efficiency, release profile, particle size control, polydispersity, scalability, reproducibility, and process complexity. Results: Batch-based techniques, such as thin-film hydration for chitosan-coated liposomal systems, consistently provide high encapsulation efficiency, sustained drug release, and good biocompatibility. However, these methods are often associated with batch-to-batch variability, operator dependence, and limited scalability. In contrast, continuous manufacturing approaches, including microfluidic mixing, nanostructured lipid carriers, and Quality-by-Design (QbD)\u2013guided processes, demonstrate improved control over particle size distribution and polydispersity, enhanced reproducibility, and better scalability potential. Conclusions: Manufacturing methodology is an important determinant of DCF and NSAID nanocarrier performance alongside formulation composition. Continuous manufacturing approaches offer promising improvements in reproducibility, process control, and scalability, but current evidence remains uneven across different nanocarrier classes. Further standardized comparative studies are needed to support their broader translation into clinical applications.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070877","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:00:17Z","timestamp":1784548817000},"page":"877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond Carrier Design: Fabrication Method as the Hidden Driver of NSAID Nanomedicine Performance"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6304-9950","authenticated-orcid":false,"given":"Ana-Maria Raluca","family":"Pauna","sequence":"first","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7983-3811","authenticated-orcid":false,"given":"Liliana","family":"Mititelu-Tartau","sequence":"additional","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2015-7032","authenticated-orcid":false,"given":"Angy Abu","family":"Koush","sequence":"additional","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0867-1135","authenticated-orcid":false,"given":"Roxana Ionela","family":"Vasluianu","sequence":"additional","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal Al","family":"Ashkar","sequence":"additional","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxandra Teodora","family":"Stan","sequence":"additional","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viorel","family":"Radu","sequence":"additional","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius Constantin","family":"Moraru","sequence":"additional","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7124-3179","authenticated-orcid":false,"given":"Cosmin Gabriel","family":"Popa","sequence":"additional","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana Florentina","family":"Gavril","sequence":"additional","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragos Valentin","family":"Crauciuc","sequence":"additional","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1785-5785","authenticated-orcid":false,"given":"Andreea","family":"Ludusanu","sequence":"additional","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristinel Ionel","family":"Stan","sequence":"additional","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9865-5114","authenticated-orcid":false,"given":"Alin Mihai","family":"Vasilescu","sequence":"additional","affiliation":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii No. 16 Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1185\/03007995.2010.486301","article-title":"Diclofenac: An Update on Its Mechanism of Action and Safety Profile","volume":"26","author":"Gan","year":"2010","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/cpt.794","article-title":"Cyclooxygenase Inhibition: Pain, Inflammation, and the Cardiovascular System","volume":"102","author":"Grosser","year":"2017","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s40265-015-0392-z","article-title":"Advances in NSAID Development: Evolution of Diclofenac Products Using Pharmaceutical Technology","volume":"75","author":"Altman","year":"2015","journal-title":"Drugs"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Drapi\u0144ska, P., Skulmowska-Polok, K., Cha\u0142upka, J., and Sikora, A. (2025). Sustained-Release Oral Delivery of NSAIDs and Acetaminophen: Advances and Recent Formulation Strategies-A Systematic Review. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17101264"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1172\/JCI27291","article-title":"Biological Basis for the Cardiovascular Consequences of COX-2 Inhibition: Therapeutic Challenges and Opportunities","volume":"116","author":"Grosser","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Khan, S., Andrews, K.L., and Chin-Dusting, J.P.F. (2019). Cyclo-Oxygenase (COX) Inhibitors and Cardiovascular Risk: Are Non-Steroidal Anti-Inflammatory Drugs Really Anti-Inflammatory?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174262"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Amanullah, A., Upadhyay, A., Dhiman, R., Singh, S., Kumar, A., Ahirwar, D.K., Gutti, R.K., and Mishra, A. (2022). Development and Challenges of Diclofenac-Based Novel Therapeutics: Targeting Cancer and Complex Diseases. Cancers, 14.","DOI":"10.3390\/cancers14184385"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"30488","DOI":"10.1038\/s41598-024-81414-x","article-title":"Re-design and evaluation of diclofenac-based carborane-substituted prodrugs and their anti-cancer potential","volume":"14","author":"Selg","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Danaei, M., Dehghankhold, M., Ataei, S., Hasanzadeh Davarani, F., Javanmard, R., Dokhani, A., Khorasani, S., and Mozafari, M.R. (2018). Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10020057"},{"key":"ref_10","first-page":"243","article-title":"Nanostructured lipid carriers as a drug delivery system: A comprehensive review with therapeutic applications","volume":"3","author":"Mall","year":"2025","journal-title":"Intell. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cooper, D.L., and Harirforoosh, S. (2014). Design and Optimization of PLGA-Based Diclofenac Loaded Nanoparticles. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087326"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103991","DOI":"10.1016\/j.mvr.2020.103991","article-title":"Diclofenac sodium loaded PLGA nanoparticles for inflammatory diseases with high anti-inflammatory properties at low dose: Formulation, characterization and in vivo HET-CAM analysis","volume":"130","year":"2020","journal-title":"Microvasc. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Khanal, S., Adhikari, U., Rijal, N.P., Bhattarai, S.R., Sankar, J., and Bhattarai, N. (2016). pH-Responsive PLGA Nanoparticle for Controlled Payload Delivery of Diclofenac Sodium. J. Funct. Biomater., 7.","DOI":"10.3390\/jfb7030021"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Esteruelas, G., Souto, E.B., Espina, M., Garc\u00eda, M.L., Switalska, M., Wietrzyk, J., Gliszczynska, A., and S\u00e1nchez-L\u00f3pez, E. (2022). Diclofenac Loaded Biodegradable Nanoparticles as Antitumoral and Antiangiogenic Therapy. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010102"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"P\u0103una, A.-M.R., Mititelu Tart\u0103u, L., Bogdan, M., Meca, A.-D., Popa, G.E., Pelin, A.-M., Drochioi, C.I., Pricop, D.A., and Pavel, L.L. (2023). Synthesis, characterization and biocompatibility evaluation of novel chitosan lipid micro-systems for modified release of diclofenac sodium. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020453"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"P\u0103una, A.-M.R., Mititelu Tart\u0103u, L., Vasilescu, A.M., Abu Koush, A., Stan, R.T., Moraru, M.C., Popa, C.G., Gavril, L.C., Gavril, R.F., and Crauciuc, D.V. (2025). Assessment of the Anti-Inflammatory Effectiveness of Diclofenac Encapsulated in Chitosan-Coated Lipid Microvesicles in Rats. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17050607"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Jaradat, E., Weaver, E., Meziane, A., and Lamprou, D.A. (2021). Microfluidics Technology for the Design and Formulation of Nanomedicines. Nanomaterials, 11.","DOI":"10.3390\/nano11123440"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14071","DOI":"10.1038\/s41598-024-64613-4","article-title":"Microfluidic production, stability and loading of synthetic giant unilamellar vesicles","volume":"14","author":"Ernits","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3060","DOI":"10.1039\/D5LC00194C","article-title":"Advances in Nanoparticle Synthesis Assisted by Microfluidics","volume":"25","author":"Saeed","year":"2025","journal-title":"Lab Chip"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Spandana, K.M.A., Angolkar, M., Rahamathulla, M., Thajudeen, K.Y., Ahmed, M.M., Farhana, S.A., Shivanandappa, T.B., Paramshetti, S., Osmani, R.A.M., and Natarajan, J. (2024). Box\u2013Behnken Design-Based Optimization and Evaluation of a Lipid-Based Nano Drug Delivery System for Brain Targeting of Bromocriptine. Pharmaceuticals, 17.","DOI":"10.3390\/ph17060720"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"120826","DOI":"10.1016\/j.biomaterials.2021.120826","article-title":"Microfluidic Formulation of Nanoparticles for Biomedical Applications","volume":"274","author":"Shepherd","year":"2021","journal-title":"Biomaterials"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1039\/D4LC00380B","article-title":"Microfluidic Technologies for Lipid Vesicle Generation","volume":"24","author":"Cheng","year":"2024","journal-title":"Lab Chip"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1039\/D3LC00821E","article-title":"Microfluidic synthesis of lipid-based nanoparticles for drug delivery: Recent advances and opportunities","volume":"24","author":"Mehraji","year":"2024","journal-title":"Lab Chip"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"114861","DOI":"10.1016\/j.addr.2023.114861","article-title":"Lipid nanoparticle-mediated drug delivery to the brain","volume":"197","author":"Khare","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"13039","DOI":"10.2147\/IJN.S554821","article-title":"Bridging the Gap: The Role of Advanced Formulation Strategies in the Clinical Translation of Nanoparticle-Based Drug Delivery Systems","volume":"20","author":"Herdiana","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Tiwary, P., Oswal, K., Varghese, R., and Gupta, P. (2026). Nanoparticles in Therapy and Diagnosis: A Comprehensive Review of Mechanisms, Applications, and Translational Challenges. J. Nanotheranostics, 7.","DOI":"10.3390\/jnt7020011"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2502315","DOI":"10.1002\/smll.202502315","article-title":"Nanoparticle Therapeutics in Clinical Perspective: Classification, Marketed Products, and Regulatory Landscape","volume":"21","author":"Desai","year":"2025","journal-title":"Small"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kumarasamy, R.V., Natarajan, P.M., Umapathy, V.R., Roy, J.R., Mironescu, M., and Palanisamy, C.P. (2024). Clinical applications and therapeutic potentials of advanced nanoparticles: A comprehensive review on completed human clinical trials. Front. Nanotechnol., 6.","DOI":"10.3389\/fnano.2024.1479993"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s41073-019-0064-8","article-title":"SANRA\u2014A Scale for the Quality Assessment of Narrative Review Articles","volume":"4","author":"Baethge","year":"2019","journal-title":"Res. Integr. Peer Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"113642","DOI":"10.1016\/j.jpba.2020.113642","article-title":"Analytical Characterization of Liposomes and Other Lipid Nanoparticles for Drug Delivery","volume":"192","author":"Fan","year":"2021","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_31","first-page":"7","article-title":"What We Need to Know about Liposomes as Drug Nanocarriers: An Updated Review","volume":"13","author":"Abbasi","year":"2023","journal-title":"Adv. Pharm. Bull."},{"key":"ref_32","first-page":"418","article-title":"Modulation of Anti-Inflammatory Activity via Diclofenac Sodium-Based Nanostructured-Lipid Carriers: Physical Characterization and In Vivo Assessment","volume":"23","author":"Singh","year":"2025","journal-title":"Assay. Drug Dev. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"39736","DOI":"10.1021\/acsami.2c06627","article-title":"Microfluidic Manufacturing of Liposomes: Development and Optimization by Design of Experiment and Machine Learning","volume":"14","author":"Rebollo","year":"2022","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Nazari, K., Mehta, P., Arshad, M.S., Ahmed, S., Andriotis, E.G., Singh, N., Qutachi, O., Chang, M.-W., Fatouros, D.G., and Ahmad, Z. (2020). Quality by Design Micro-Engineering Optimisation of NSAID-Loaded Electrospun Fibrous Patches. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12010002"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.apt.2010.08.010","article-title":"The Effects of RESS Parameters on the Diclofenac Particle Size","volume":"22","author":"Hezave","year":"2011","journal-title":"Adv. Powder Technol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Jadhav, S., Kaur, A., and Bansal, A.K. (2020). Comparison of Downstream Processing of Nanocrystalline Solid Dispersion and Nanosuspension of Diclofenac Acid to Develop Solid Oral Dosage Form. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12111015"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ijbiomac.2016.02.033","article-title":"Optimizing Indomethacin-Loaded Chitosan Nanoparticle Size, Encapsulation, and Release Using Box\u2013Behnken Experimental Design","volume":"87","author":"Kalam","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_38","first-page":"4071818","article-title":"Improved Analgesic and Anti-Inflammatory Effect of Diclofenac Sodium by Topical Nanoemulgel: Formulation Development\u2014In Vitro and In Vivo Studies","volume":"2020","author":"Shadab","year":"2020","journal-title":"J. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"105544","DOI":"10.1016\/j.jddst.2024.105544","article-title":"Diclofenac derivatives as promising anticancer and anti-inflammatory drug: Synthesis, formulations, and pharmacokinetics","volume":"95","author":"Alshargabi","year":"2024","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zafar, A., Alruwaili, N.K., Imam, S.S., Yasir, M., Alsaidan, O.A., Alquraini, A., Rawaf, A., Alsuwayt, B., Anwer, M.K., and Alshehri, S. (2022). Development and Optimization of Nanolipid-Based Formulation of Diclofenac Sodium: In Vitro Characterization and Preclinical Evaluation. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14030507"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"124641","DOI":"10.1016\/j.ijpharm.2024.124641","article-title":"Production of liposomes by microfluidics: The impact of post-manufacturing dilution on drug encapsulation and lipid loss","volume":"664","author":"Pittiu","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105359","DOI":"10.1016\/j.jddst.2024.105359","article-title":"Preparation characterization of diclofenac transdermal patch using ethyl cellulose polyvinyl alcohol by electrospinning","volume":"92","author":"Akbari","year":"2024","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_43","first-page":"60","article-title":"New Product Development, Evaluation, with Optimization Diclofenac Transport for Gout","volume":"8","author":"Samanthula","year":"2025","journal-title":"Vasc. Endovasc. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.52711\/0974-360X.2025.00320","article-title":"Design and optimization of nanoemulsion system by simplex lattice design method to improve solubility of topical diclofenac sodium","volume":"18","author":"Nahdhia","year":"2025","journal-title":"Res. J. Pharm. Technol."},{"key":"ref_45","first-page":"610","article-title":"Repurposing Drugs in Oncology (ReDO)\u2014Diclofenac as an anti-cancer agent","volume":"10","author":"Pantziarka","year":"2016","journal-title":"Ecancermedicalscience"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1007\/s12668-026-02520-w","article-title":"pH-Responsive Eudragit-Coated \u03b2-Cyclodextrin-Chitosan Nanoparticles for Controlled and Site-Specific Oral Delivery of Indomethacin: Systematic Optimization and in vitro Study","volume":"16","author":"Parker","year":"2026","journal-title":"BioNanoScience"},{"key":"ref_47","unstructured":"International Council for Harmonisation (2022). ICH Q13: Continuous Manufacturing of Drug Substances and Drug Products, International Council for Harmonisation."},{"key":"ref_48","unstructured":"International Council for Harmonisation (2023). ICH Q9(R1): Quality Risk Management, International Council for Harmonisation."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/7\/877\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T16:18:07Z","timestamp":1784650687000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/7\/877"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":48,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["pharmaceutics18070877"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18070877","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]}}}