{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T21:02:17Z","timestamp":1777410137322,"version":"3.51.4"},"reference-count":60,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Baricitinib, a selective JAK1\/JAK2 inhibitor, shows therapeutic potential in psoriasis; however, its oral use is associated with systemic adverse effects, encouraging the development of topical formulations. This study aimed at evaluating the influence of petrolatum type on the stability, biopharmaceutical performance, and therapeutic activity of lipid-based formulations containing Baricitinib. Methods: Formulations were prepared with Labrafac\u00ae Lipophile WL 1349 (L) and either liquid (LLV) or solid (LSV) petrolatum at 30% and 60% w\/w. Stability, rheology, spreadability, in vitro release, ex vivo permeation, and skin retention were evaluated, along with the safety and efficacy in HET-CAM and imiquimod-induced psoriasis murine models. Results: Only 30% petrolatum formulations remained stable for 60 days. LLV exhibited Newtonian flow, higher spreadability, sustained release (83.7% at 50 h), and superior skin retention (94 \u00b5g\/g of skin\/cm2), whereas LSV showed pseudoplastic behavior, lower spreadability, and reduced release (47.4% at 50 h). Both formulations were non-irritant and improved stratum corneum hydration while reducing transepidermal water loss. In vivo, both reduced erythema, epidermal thickening, edema, and histological alterations, confirming anti-inflammatory efficacy. Conclusions: These results demonstrate that the vehicle occlusivity decisively modulates baricitinib\u2019s release and activity. LLV formulation favored drug retention and enhanced permeation at 24 h. Overall, excipient selection is important in designing safe and effective topical JAK inhibitor formulations.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010008","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T14:27:51Z","timestamp":1766586471000},"page":"8","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Impact of Vehicle Occlusivity on Skin Delivery and Activity of a Janus Kinase Inhibitor: Comparison of Oil-Based Formulations"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9178-635X","authenticated-orcid":false,"given":"Paulo","family":"Sarango-Granda","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica, Facultad de Ciencias Exactas y Naturales, Universidad T\u00e9cnica Particular de Loja (UTPL), Paris SN y Praga, Loja 1101607, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4799-6362","authenticated-orcid":false,"given":"Roya","family":"Mohammadi-Meyabadi","sequence":"additional","affiliation":[{"name":"Departament de Farm\u00e0cia i Tecnologia Farmac\u00e8utica, i Fisicoqu\u00edmica, Facultat de Farm\u00e0cia i Ci\u00e8ncies de l\u2019Alimentaci\u00f3, Universitat de Barcelona (UB), Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2669-7006","authenticated-orcid":false,"given":"Antonio J.","family":"Braza","sequence":"additional","affiliation":[{"name":"Departament de Farm\u00e0cia i Tecnologia Farmac\u00e8utica, i Fisicoqu\u00edmica, Facultat de Farm\u00e0cia i Ci\u00e8ncies de l\u2019Alimentaci\u00f3, Universitat de Barcelona (UB), Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8148-9482","authenticated-orcid":false,"given":"Lilian","family":"Sosa","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones en Microbiolog\u00eda (IIM), Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de Honduras (UNAH), Tegucigalpa 11101, Honduras"},{"name":"Centro Experimental en Biociencia (CENBIO), Facultad de Ciencias Qu\u00edmicas y Farmacia, Universidad Nacional Aut\u00f3noma de Honduras (UNAH), Tegucigalpa 11101, Honduras"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9238-187X","authenticated-orcid":false,"given":"Joaquim","family":"Su\u00f1er-Carb\u00f3","sequence":"additional","affiliation":[{"name":"Departament de Farm\u00e0cia i Tecnologia Farmac\u00e8utica, i Fisicoqu\u00edmica, Facultat de Farm\u00e0cia i Ci\u00e8ncies de l\u2019Alimentaci\u00f3, Universitat de Barcelona (UB), Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"},{"name":"Institut de Nanoci\u00e8ncia i Nanotecnologia, Universitat de Barcelona (UB), Av. Diagonal 645, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9316-8459","authenticated-orcid":false,"given":"Mireia","family":"Mallandrich","sequence":"additional","affiliation":[{"name":"Departament de Farm\u00e0cia i Tecnologia Farmac\u00e8utica, i Fisicoqu\u00edmica, Facultat de Farm\u00e0cia i Ci\u00e8ncies de l\u2019Alimentaci\u00f3, Universitat de Barcelona (UB), Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"},{"name":"Institut de Nanoci\u00e8ncia i Nanotecnologia, Universitat de Barcelona (UB), Av. Diagonal 645, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-4821","authenticated-orcid":false,"given":"Ana Cristina","family":"Calpena","sequence":"additional","affiliation":[{"name":"Departament de Farm\u00e0cia i Tecnologia Farmac\u00e8utica, i Fisicoqu\u00edmica, Facultat de Farm\u00e0cia i Ci\u00e8ncies de l\u2019Alimentaci\u00f3, Universitat de Barcelona (UB), Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"},{"name":"Institut de Nanoci\u00e8ncia i Nanotecnologia, Universitat de Barcelona (UB), Av. Diagonal 645, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41419-022-04523-3","article-title":"Advances in the Pathogenesis of Psoriasis: From Keratinocyte Perspective","volume":"13","author":"Zhou","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gao, Y., Xu, T., Wang, Y., Hu, Y., Yin, S., Qin, Z., and Yu, H. (2025). Pathophysiology and Treatment of Psoriasis: From Clinical Practice to Basic Research. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17010056"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hao, Y., Zhu, Y., Zou, S., Zhou, P., Hu, Y., Zhao, Q., Gu, L., Zhang, H., Wang, Z., and Li, J. (2021). Metabolic Syndrome and Psoriasis: Mechanisms and Future Directions. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.711060"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.15420\/ecr.2020.15.R2","article-title":"The Association Between Psoriasis and Cardiovascular Diseases","volume":"16","author":"Zwain","year":"2021","journal-title":"Eur. Cardiol."},{"key":"ref_5","first-page":"e9708","article-title":"Association Between Psoriasis and Depression: A Traditional Review","volume":"12","author":"Sahi","year":"2020","journal-title":"Cureus"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1468-3083.2009.03389.x","article-title":"European S3-Guidelines on the Systemic Treatment of Psoriasis Vulgaris","volume":"23","author":"Pathirana","year":"2009","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"113508","DOI":"10.1016\/j.intimp.2024.113508","article-title":"From Manifestations to Innovations: A Deep Dive into Psoriasis, Its Clinical Diversity, Conventional Treatments, and Emerging Therapeutic Paradigms","volume":"143","author":"Garg","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"460","DOI":"10.5114\/ada.2021.108445","article-title":"Treatments in Psoriasis: From Standard Pharmacotherapy to Nanotechnology Therapy","volume":"39","author":"Zhu","year":"2022","journal-title":"Postep. Dermatol. Alergol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41584-024-01153-1","article-title":"JAK Inhibitor Selectivity: New Opportunities, Better Drugs?","volume":"20","author":"Virtanen","year":"2024","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kraev, K., Geneva-Popova, M.G., Hristov, B.K., Uchikov, P.A., Belova-Popova, S.D., Kraeva, M.I., Basheva-Kraeva, Y.M., Stoyanova, N.S., Mitkova-Hristova, V.T., and Koleva-Ivanova, M.S. (2023). Examining the Safety Profile of Janus Kinase (JAK) Inhibitors in the Management of Immune-Mediated Diseases: A Comprehensive Review. Life, 13.","DOI":"10.3390\/life13122244"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"113568","DOI":"10.1016\/j.intimp.2024.113568","article-title":"Baricitinib Inhibits the Activation of Innate Immune Cells and Exerts Therapeutic Effects on Acute Peritonitis and Systemic Inflammatory Response Syndrome","volume":"143","author":"Hao","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1111\/bjd.14403","article-title":"A Randomized Phase 2b Trial of Baricitinib, an Oral Janus Kinase (JAK) 1\/JAK2 Inhibitor, in Patients with Moderate-to-severe Psoriasis","volume":"174","author":"Papp","year":"2016","journal-title":"Br. J. Dermatol"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1002\/art.41580","article-title":"Venous Thromboembolism Risk with JAK Inhibitors: A Meta-Analysis","volume":"73","author":"Yates","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1002\/art.40841","article-title":"Cardiovascular Safety During Treatment with Baricitinib in Rheumatoid Arthritis","volume":"71","author":"Taylor","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jaad.2018.04.018","article-title":"Topical Janus Kinase Inhibitors: A Review of Applications in Dermatology","volume":"79","author":"Hosking","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4128","DOI":"10.4103\/jfmpc.jfmpc_112_24","article-title":"JAK 1-3 Inhibitors and TYK-2 Inhibitors in Dermatology: Practical Pearls for the Primary Care Physician","volume":"13","author":"Beard","year":"2024","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.jaad.2011.12.018","article-title":"Preliminary Clinical Activity of a Topical JAK1\/2 Inhibitor in the Treatment of Psoriasis","volume":"67","author":"Punwani","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"119655","DOI":"10.1016\/j.lfs.2021.119655","article-title":"Effect of Baricitinib on TPA-Induced Psoriasis like Skin Inflammation","volume":"279","year":"2021","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mohammadi-Meyabadi, R., Mallandrich, M., Beirampour, N., Garr\u00f3s, N., Espinoza, L.C., Sosa, L., Su\u00f1er-Carb\u00f3, J., Rodr\u00edguez-Lagunas, M.J., Gardu\u00f1o-Ram\u00edrez, M.L., and Calpena-Campmany, A.C. (2024). Lipid-Based Formulation of Baricitinib for the Topical Treatment of Psoriasis. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16101287"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.1055\/s-0042-1751036","article-title":"Lipid-Based Nanocarrier Systems for Drug Delivery: Advances and Applications","volume":"4","author":"Zhao","year":"2022","journal-title":"Pharm. Front."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Gaggero, A., Marko, V., Jeremic, D., Tetyczka, C., Caisse, P., and Afonso Urich, J.A. (2025). AQbD-Based UPLC-ELSD Method for Quantifying Medium Chain Triglycerides in LabrafacTM WL 1349 for Nanoemulsion Applications. Molecules, 30.","DOI":"10.3390\/molecules30030486"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.jaad.2023.06.010","article-title":"Petroleum Jelly: A Comprehensive Review of Its History, Uses, and Safety","volume":"90","author":"Kamrani","year":"2024","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ijpharm.2018.02.016","article-title":"Study of Petrolatum Structure: Explaining Its Variable Rheological Behavior","volume":"540","author":"Landman","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_24","unstructured":"National Center for Biotechnology (2025, November 13). Information PubChem Compound Summary for CID 44205240, Baricitinib, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/44205240."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mohammadi-Meyabadi, R., Beirampour, N., Garr\u00f3s, N., Alvarado, H.L., Lim\u00f3n, D., Silva-Abreu, M., Calpena, A.C., and Mallandrich, M. (2022). Assessing the Solubility of Baricitinib and Drug Uptake in Different Tissues Using Absorption and Fluorescence Spectroscopies. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14122714"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.tiv.2018.04.009","article-title":"Transepidermal Water Loss and Skin Conductance as Barrier Integrity Tests","volume":"51","author":"Zhang","year":"2018","journal-title":"Toxicol. Vitr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1007\/s11095-016-1955-8","article-title":"Estimating Maximal In Vitro Skin Permeation Flux from Studies Using Non-Sink Receptor Phase Conditions","volume":"33","author":"Yousef","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106168","DOI":"10.1016\/j.tiv.2025.106168","article-title":"Assessment of Ocular Irritation Potential of Moisturizing and Sunscreen Cosmetic Creams Marketed in Algeria Using the HET-CAM Test","volume":"111","author":"Imane","year":"2026","journal-title":"Toxicol. Vitr."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sousa, G.D., De Souza Dantas, I.M.F., De Santana, D.P., and Leal, L.B. (2018). New Oils for Cosmetic O\/W Emulsions: In Vitro\/In Vivo Evaluation. Cosmetics, 5.","DOI":"10.3390\/cosmetics5010006"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.jaad.2008.02.006","article-title":"Classification of Facial Psoriasis Based on the Distributions of Facial Lesions","volume":"58","author":"Woo","year":"2008","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_31","first-page":"96","article-title":"Facial Psoriasis: Hard to Hide a Serious Psoriasis","volume":"2","author":"Wahab","year":"2020","journal-title":"J. Bangladesh Assoc. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/jps.21088","article-title":"Alternative Methods for Eye and Skin Irritation Tests: An Overview","volume":"97","author":"Vinardell","year":"2008","journal-title":"J. Pharm. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105255","DOI":"10.1016\/j.tiv.2021.105255","article-title":"Comparison of the Different Protocols of the Hen\u2019s Egg Test-Chorioallantoic Membrane (HET-CAM) by Evaluating the Eye Irritation Potential of Surfactants","volume":"78","author":"Silva","year":"2022","journal-title":"Toxicol. Vitr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.bjp.2015.11.006","article-title":"In Vitro and in vivo Evaluation of Efficacy and Safety of Photoprotective Formulations Containing Antioxidant Extracts","volume":"26","author":"Mansur","year":"2016","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.jaci.2019.08.042","article-title":"INCB 18424-206 Study Investigators Treatment of Atopic Dermatitis with Ruxolitinib Cream (JAK1\/JAK2 Inhibitor) or Triamcinolone Cream","volume":"145","author":"Kim","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_36","unstructured":"(2001). Especificaciones t\u00e9cnicas para la producci\u00f3n, cuidado y uso de los animales de laboratorio (Standard No. NOM-062-ZOO-1999)."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1007\/s13346-024-01732-5","article-title":"Topical Delivery of Baricitinib-Impregnated Nanoemulgel: A Promising Platform for Inhibition of JAK\u2014STAT Pathway for the Effective Management of Atopic Dermatitis","volume":"15","author":"Nene","year":"2024","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_38","first-page":"75","article-title":"Designing a Topical Nanoliposomal Formulation of Ruxolitinib Phosphate","volume":"29","author":"Naeimifar","year":"2022","journal-title":"Pharm. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/bjd\/ljad098","article-title":"Efficacy and Safety of Topical Brepocitinib Cream for Mild-to-Moderate Chronic Plaque Psoriasis: A Phase IIb Randomized Double-Blind Vehicle-Controlled Parallel-Group Study","volume":"189","author":"Landis","year":"2023","journal-title":"Br. J. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Papp, K.A., Bissonnette, R., Gooderham, M., Feldman, S.R., Iversen, L., Soung, J., Draelos, Z., Mamolo, C., Purohit, V., and Wang, C. (2016). Treatment of Plaque Psoriasis with an Ointment Formulation of the Janus Kinase Inhibitor, Tofacitinib: A Phase 2b Randomized Clinical Trial. BMC Dermatol., 16.","DOI":"10.1186\/s12895-016-0051-4"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1208\/s12248-010-9185-1","article-title":"DDSolver: An Add-in Program for Modeling and Comparison of Drug Dissolution Profiles","volume":"12","author":"Zhang","year":"2010","journal-title":"AAPS J."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mijaljica, D., Townley, J.P., Klionsky, D.J., Spada, F., and Lai, M. (2025). The Origin, Intricate Nature, and Role of the Skin Surface pH (pHSS) in Barrier Integrity, Eczema, and Psoriasis. Cosmetics, 12.","DOI":"10.3390\/cosmetics12010024"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Langley, N., Michniak-Kohn, B., and Osborne, D.W. (2019). Rheological Characterization in the Development of Topical Drug Products. The Role of Microstructure in Topical Drug Product Development, Springer International Publishing.","DOI":"10.1007\/978-3-030-17355-5"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Manian, M., Jain, P., Vora, D., and Banga, A.K. (2022). Formulation and Evaluation of the In Vitro Performance of Topical Dermatological Products Containing Diclofenac Sodium. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14091892"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Torres, A., Almeida, I.F., and Oliveira, R. (2024). An Overview of Proprietary Vehicles\/Bases for Topical Compounding Medicines and Cosmetics. Cosmetics, 11.","DOI":"10.3390\/cosmetics11010016"},{"key":"ref_46","unstructured":"Li, S.K. (2013). Transdermal Delivery Technologies. Encyclopedia of Pharmaceutical Science and Technology, Six Volume Set (Print), CRC Press."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jconrel.2018.03.003","article-title":"In Vitro and Ex Vivo Correlation of Drug Release from Ophthalmic Ointments","volume":"276","author":"Bao","year":"2018","journal-title":"J. Control Release"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1002\/ddr.10213","article-title":"Optimization of Drug Release from Dermatological Semisolid Preparations","volume":"59","author":"Eros","year":"2003","journal-title":"Drug Dev. Res."},{"key":"ref_49","unstructured":"European Medicines Agency (2018). Guideline on Quality and Equivalence of Locally Applied and Locally Acting Cutaneous Products, European Medicines Agency."},{"key":"ref_50","unstructured":"Heaney, J. (2014). Diffusion Method Development Guidelines (WP0001 A), JASCO Technical Application."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Virani, A., Puri, V., Mohd, H., and Michniak-Kohn, B. (2023). Effect of Penetration Enhancers on Transdermal Delivery of Oxcarbazepine, an Antiepileptic Drug Using Microemulsions. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010183"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ijpharm.2005.07.014","article-title":"Skin Permeation: The Years of Enlightenment","volume":"305","author":"Hadgraft","year":"2005","journal-title":"Int. J. Pharm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jconrel.2012.09.017","article-title":"Approaches for Breaking the Barriers of Drug Permeation through Transdermal Drug Delivery","volume":"164","author":"Alexander","year":"2012","journal-title":"J. Control Release"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/j.1468-2494.2012.00747.x","article-title":"Rational formulation design","volume":"34","author":"Lane","year":"2012","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Silva-Abreu, M., Sosa, L., Espinoza, L.C., F\u00e1brega, M.-J., Rodr\u00edguez-Lagunas, M.J., Mallandrich, M., Calpena, A.C., Gardu\u00f1o-Ram\u00edrez, M.L., and Rinc\u00f3n, M. (2023). Efficacy of Apremilast Gels in Mouse Model of Imiquimod-Induced Psoriasis Skin Inflammation. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15102403"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Bakhrushina, E.O., Shumkova, M.M., Avdonina, Y.V., Ananian, A.A., Babazadeh, M., Pouya, G., Grikh, V.V., Zubareva, I.M., Kosenkova, S.I., and Krasnyuk, I.I. (2025). Transdermal Drug Delivery Systems: Methods for Enhancing Skin Permeability and Their Evaluation. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17070936"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"128","DOI":"10.29262\/ram.v67i2.730","article-title":"Emolientes: Beneficios, elementos clave y aplicaci\u00f3n cl\u00ednica","volume":"67","author":"Cardona","year":"2020","journal-title":"Rev. Alerg. Mex."},{"key":"ref_58","unstructured":"European Medicines Agency (2025, November 03). Guideline on Non-Clinical Local Tolerance Testing of Medicinal Products. EMA\/CHMP\/SWP\/2145\/2000. Available online: https:\/\/www.ema.europa.eu\/en\/non-clinical-local-tolerance-testing-medicinal-products-scientific-guideline."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ordo\u00f1ez-Toro, A., Montero-Vilchez, T., Mu\u00f1oz-Baeza, J., Sanabria-De-la-Torre, R., Buendia-Eisman, A., and Arias-Santiago, S. (2022). The Assessment of Skin Homeostasis Changes after Using Different Types of Excipients in Healthy Individuals. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph192416678"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Jabeen, M., Boisgard, A.-S., Danoy, A., El Kholti, N., Salvi, J.-P., Boulieu, R., Fromy, B., Verrier, B., and Lamrayah, M. (2020). Advanced Characterization of Imiquimod-Induced Psoriasis-Like Mouse Model. 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