{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T23:04:47Z","timestamp":1770073487618,"version":"3.49.0"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology (FCT, Portugal) for the financial support to CIQUP","award":["UIDB\/00081\/2025"],"award-info":[{"award-number":["UIDB\/00081\/2025"]}]},{"name":"IMS-Institute of Molecular Sciences","award":["LA\/P\/0056\/2020"],"award-info":[{"award-number":["LA\/P\/0056\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Applied Sciences"],"abstract":"<jats:p>Oral mucositis is an inflammatory and ulcerative disease that affects patients undergoing cancer treatment, namely chemotherapy and radiotherapy, significantly compromising their quality of life. Despite its high incidence and clinical impact, current therapeutic options remain limited, reinforcing the need for new treatment approaches. In this context, the Instituto Portugu\u00eas de Oncologia do Porto FG, EPE (IPO-Porto) developed an innovative mouthwash containing dexamethasone sodium phosphate (DSP), ascorbic acid, and sodium hyaluronate. In this work the physicochemical stability of this formulation was evaluated to ensure its quality and safety as compounded medicine. Exploratory studies were performed under accelerated aging conditions (40 \u00b1 2 \u00b0C), followed by stability studies under real-time conditions (20 \u00b1 2 \u00b0C) and refrigeration conditions (4 \u00b1 2 \u00b0C), as well as in-use stability studies simulating daily patient handling. At each sampling time, physicochemical characterization was carried out (pH, color, odor, and precipitate formation) as well as the DSP quantification using high-performance liquid chromatography. The acceptable range of 90.0\u2013110.0%, compared to the initial concentration of DSP, was used as the primary stability criterion. Results showed that the formulation remained stable at high temperatures (40 \u00b0C), on short exposures times (\u22646 h), and for 30 days at 4 \u00b0C in closed amber glass bottles. In-use stability studies performed during the 7 days after opening (considering three daily applications) showed that the DSP concentration remained above 90%. The results obtained enabled us to establish a definition of storage conditions and beyond-use recommendations, since they showed that the prepared formulation is stable when stored under refrigeration. Further studies are currently being developed with a view to its clinical use as a compounded mouthwash in a hospital setting for the treatment of oral mucositis.<\/jats:p>","DOI":"10.3390\/app16031491","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:00:47Z","timestamp":1770033647000},"page":"1491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stability Study of a New Compounded Medicine for the Treatment of Oral Mucositis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4478-0213","authenticated-orcid":false,"given":"Mariana","family":"Neto","sequence":"first","affiliation":[{"name":"CIQUP-IMS, ISEP, Polytechnic of Porto, Rua Dr. Bernardino de Almeida 431, 4249-015 Porto, Portugal"}]},{"given":"Susana","family":"Pinto","sequence":"additional","affiliation":[{"name":"Pharmaceutical Services, Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto. CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Ermelinda M.P.J.","family":"Garrido","sequence":"additional","affiliation":[{"name":"CIQUP-IMS, ISEP, Polytechnic of Porto, Rua Dr. Bernardino de Almeida 431, 4249-015 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1498-048X","authenticated-orcid":false,"given":"Isabel F.","family":"Almeida","sequence":"additional","affiliation":[{"name":"UCIBIO, i4HB, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8981-231X","authenticated-orcid":false,"given":"Jorge","family":"Garrido","sequence":"additional","affiliation":[{"name":"CIQUP-IMS, ISEP, Polytechnic of Porto, Rua Dr. Bernardino de Almeida 431, 4249-015 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"ref_1","unstructured":"(2025, December 09). Eurostat Cancer Statistics. Available online: https:\/\/ec.europa.eu\/eurostat\/statistics-explained\/index.php?title=Cancer_statistics."},{"key":"ref_2","unstructured":"OECD (2025). EU Country Cancer Profile: Portugal 2025, OECD Publishing."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s12672-025-02198-8","article-title":"Advancements and Limitations in Traditional Anti-Cancer Therapies: A Comprehensive Review of Surgery, Chemotherapy, Radiation Therapy, and Hormonal Therapy","volume":"16","author":"Zafar","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101300","DOI":"10.1016\/j.disamonth.2021.101300","article-title":"Oral Mucositis: Current Knowledge and Future Directions","volume":"68","author":"Shetty","year":"2022","journal-title":"Disease-a-Month"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.21037\/tcr.2020.02.77","article-title":"Impact of Oral Mucositis on Quality of Life in Patients Undergoing Oncological Treatment: A Systematic Review","volume":"9","author":"Gopinath","year":"2020","journal-title":"Transl. Cancer Res."},{"key":"ref_6","first-page":"3249","article-title":"Prevalence of Oral Mucositis, Dry Mouth, and Dysphagia in Advanced Cancer Patients","volume":"23","author":"Mercadante","year":"2015","journal-title":"Support. Care Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1200\/JOP.19.00652","article-title":"Management of Cancer Therapy\u2013Associated Oral Mucositis","volume":"16","author":"Brown","year":"2020","journal-title":"JCO Oncol. Pract."},{"key":"ref_8","first-page":"57","article-title":"The Broadening Scope of Oral Mucositis and Oral Ulcerative Mucosal Toxicities of Anticancer Therapies","volume":"72","author":"Elad","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3892\/mco.2014.253","article-title":"Oral Mucositis in Cancer Treatment: Natural History, Prevention and Treatment","volume":"2","year":"2014","journal-title":"Mol. Clin. Oncol."},{"key":"ref_10","first-page":"201","article-title":"V Treatment of Oral Mucositis Due to Chemotherapy","volume":"8","year":"2016","journal-title":"J. Clin. Exp. Dent."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102883","DOI":"10.1016\/j.ctrv.2025.102883","article-title":"Managing Strategies of Chemotherapy and Radiotherapy-Induced Oral Mucositis","volume":"133","author":"Wu","year":"2025","journal-title":"Cancer Treat. Rev."},{"key":"ref_12","unstructured":"Bell, A., and Kasi, A. (2023). Oral Mucositis. StatPearls, StatPearls Publishing."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.soncn.2007.05.005","article-title":"Prevention and Management of Oral Mucositis in Patients With Cancer","volume":"23","author":"Eilers","year":"2007","journal-title":"Semin. Oncol. Nurs."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4423","DOI":"10.1002\/cncr.33100","article-title":"MASCC\/ISOO Clinical Practice Guidelines for the Management of Mucositis Secondary to Cancer Therapy","volume":"126","author":"Elad","year":"2020","journal-title":"Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"151252","DOI":"10.1016\/j.soncn.2022.151252","article-title":"Clinical Updates in Mucositis-Related Symptom Management","volume":"38","author":"Isozaki","year":"2022","journal-title":"Semin. Oncol. Nurs."},{"key":"ref_16","first-page":"lgz011","article-title":"Oral Mucositis Due to High-Dose Chemotherapy and\/or Head and Neck Radiation Therapy","volume":"2019","author":"Lalla","year":"2019","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_17","first-page":"7205","article-title":"Anti-Inflammatory Mouthwashes for the Prevention of Oral Mucositis in Cancer Therapy: An Integrative Review and Meta-Analysis","volume":"30","author":"Thornton","year":"2022","journal-title":"Support. Care Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.rdc.2015.08.002","article-title":"Corticosteroids","volume":"42","author":"Ramamoorthy","year":"2016","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Synaridou, M.S., Andriotis, E.G., Zacharis, C.K., Fatouros, D.G., and Markopoulou, C.K. (2020). Solid Dosage Forms of Dexamethasone Sodium Phosphate Intended for Pediatric Use: Formulation and Stability Studies. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12040354"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"122609","DOI":"10.1016\/j.jchromb.2021.122609","article-title":"Rapid and Simultaneous Determination of Dexamethasone and Dexamethasone Sodium Phosphate Using HPLC-UV: Application in Microneedle-Assisted Skin Permeation and Deposition Studies","volume":"1170","author":"Duarah","year":"2021","journal-title":"J. Chromatogr. B"},{"key":"ref_21","first-page":"7963","article-title":"The Effects of a Combination Oral Spray (Mucosamin\u00ae) for the Prevention of Oral Mucositis in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation: A Double Blind Randomized Clinical Trial","volume":"30","author":"Shahrabi","year":"2022","journal-title":"Support. Care Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1111\/jop.13471","article-title":"Dexamethasone Solution and Dexamethasone in MucoloxTM for the Treatment of Oral Inflammatory Ulcerative Diseases: A Phase II Randomized Clinical Trial","volume":"52","author":"Lodolo","year":"2023","journal-title":"J. Oral Pathol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e9886","DOI":"10.1590\/1414-431x20209886","article-title":"Hyaluronic Acid versus Dexamethasone for the Treatment of Recurrent Aphthous Stomatitis in Children: Efficacy and Safety Analysis","volume":"53","author":"Yang","year":"2020","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_24","first-page":"494","article-title":"Prospective Longitudinal Analysis of Clinical and Immunological Risk Factors Associated with Oral and Gastrointestinal Mucositis Following Autologous Stem Cell Transplant in Adults","volume":"31","author":"Wong","year":"2023","journal-title":"Support. Care Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"120884","DOI":"10.1016\/j.carbpol.2023.120884","article-title":"Hyaluronic Acid Modified Oral Drug Delivery System with Mucoadhesiveness and Macrophage-Targeting for Colitis Treatment","volume":"313","author":"Zhang","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref_26","first-page":"430","article-title":"Effects of L-Glutamine and Hyaluronic Acid Associated with Photobiomodulation on Oral Mucositis: A Randomized Clinical Trial","volume":"33","author":"Martins","year":"2025","journal-title":"Support. Care Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1111\/jop.13636","article-title":"Mucosamin Spray for the Prevention of Oral Mucositis in Cancer Patients Receiving Chemotherapy: A Retrospective Cohort Study","volume":"54","author":"Colella","year":"2025","journal-title":"J. Oral Pathol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/jcp.24908","article-title":"A Hyaluronic Acid-Based Compound Inhibits Fibroblast Senescence Induced by Oxidative Stress In Vitro and Prevents Oral Mucositis In Vivo","volume":"230","author":"Cirillo","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/s41419-023-05934-6","article-title":"High Molecular Weight Hyaluronic Acid Drastically Reduces Chemotherapy-Induced Mucositis and Apoptotic Cell Death","volume":"14","author":"Mohammed","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_30","unstructured":"Yoshioka, S., and Stella, V.J. (2002). Stability of Drugs and Dosage Forms, Springer."},{"key":"ref_31","unstructured":"Rowe, R.C., Sheskey, P.J., and Weller, P.J. (2006). Handbook of Pharmaceutical Excipients, Pharmaceutical Press."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1177\/0018578719888912","article-title":"Physical and Chemical Stability of Dexamethasone Sodium Phosphate in Intravenous Admixtures Used to Prevent Chemotherapy-Induced Nausea and Vomiting","volume":"56","author":"Buga","year":"2021","journal-title":"Hosp. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Carmo, F.J.R., Salote, E.P.Z., Valente, A.J.M., Ribeiro, A.C.F., Nicolau, P.M.G., and Fangaia, S.I.G. (2025). Diffusion of Sodium Hyaluronate in Artificial Saliva to Optimize Its Topical Application. Molecules, 30.","DOI":"10.3390\/molecules30102140"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1093\/chromsci\/bmae028","article-title":"Development and Validation of a RP-HPLC Method for the Simultaneous Determination of Silver Sulfadiazine and Sodium Hyaluronate in the Presence of Methyl and Propyl Paraben in a Pharmaceutical Cream for Burns","volume":"62","author":"Boltia","year":"2024","journal-title":"J. Chromatogr. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"105","DOI":"10.4314\/tjpr.v10i1.66549","article-title":"Rapid and Reliable HPLC Method for the Determination of Vitamin C in Pharmaceutical Samples","volume":"10","author":"Mitic","year":"2011","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"532","DOI":"10.5530\/ijper.52.3.61","article-title":"Oral Mucositis Severity Assessment by Supplementation of High Dose Ascorbic Acid During Chemo and\/or Radiotherapy of Oro-Pharyngeal Cancers\u2014A Pilot Project","volume":"52","author":"Chaitanya","year":"2018","journal-title":"Indian J. Pharm. Educ. Res."},{"key":"ref_37","unstructured":"The United States Pharmacopeial Convention (2022). United States Pharmacopeia (USP) General Chapter \u2329795\u232a Pharmaceutical Compounding\u2014Nonsterile Preparations. United States Pharmacopeia and National Formulary (USP\u2013NF), The United States Pharmacopeial Convention."},{"key":"ref_38","first-page":"164","article-title":"Strength and Stability Testing for Compounded Preparations","volume":"78","author":"Allen","year":"2014","journal-title":"US Pharmacop."},{"key":"ref_39","unstructured":"European Directorate for the Quality of Medicines & HealthCare (2021). Dexamethasone Sodium Phosphate. European Pharmacopoeia, Council of Europe."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Borman, P., and Elder, D. (2017). Q2(R1) Validation of Analytical Procedures. ICH Quality Guidelines, Wiley.","DOI":"10.1002\/9781118971147.ch5"},{"key":"ref_41","unstructured":"United States Pharmacopeial Convention (2006). The United States Pharmacopeia: USP 30; The National Formulary: NF 25, United States Pharmacopeial Convention."},{"key":"ref_42","first-page":"606","article-title":"Validation of Stability-Indicating HPLC Methods for Pharmaceuticals: Overview, Methodologies, and Case Studies","volume":"38","author":"Dong","year":"2020","journal-title":"LCGC N. Am."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.jpha.2013.02.001","article-title":"Determination of Sodium Hyaluronate in Pharmaceutical Formulations by HPLC\u2013UV","volume":"3","author":"Ruckmani","year":"2013","journal-title":"J. Pharm. Anal."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1351\/pac199365040819","article-title":"Nomenclature for Chromatography","volume":"65","author":"Recommendations","year":"1993","journal-title":"Pure Appl. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s00769-002-0487-6","article-title":"Linearity of Calibration Curves: Use and Misuse of the Correlation Coefficient","volume":"7","author":"Elskens","year":"2002","journal-title":"Accredit. Qual. Assur."},{"key":"ref_46","unstructured":"International Conference on Harmonisation (2005). ICH Q2(R1)\u2014Validation of Analytical Procedures: Text and Methodology, International Conference on Harmonisation."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jpainsymman.2005.01.018","article-title":"Compatibility and Stability of Dexamethasone Sodium Phosphate and Ketamine Hydrochloride Subcutaneous Infusions in Polypropylene Syringes","volume":"30","author":"Watson","year":"2005","journal-title":"J. Pain Symptom Manag."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"120092","DOI":"10.1016\/j.ijpharm.2020.120092","article-title":"Stabilization of Vitamin C in Emulsions of Liquid Crystalline Structures","volume":"592","author":"Bolzinger","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_49","unstructured":"Committee for Proprietary Medicinal Products (2001). Note for Guidance on In-Use Stability Testing of Human Medicinal Products, Committee for Proprietary Medicinal Products."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1208\/s12249-024-02882-y","article-title":"Understand the Stabilization Engineering of Ascorbic Acid, Mapping the Scheme for Stabilization, and Advancement","volume":"25","author":"Shelke","year":"2024","journal-title":"AAPS PharmSciTech"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Yin, X., Chen, K., Cheng, H., Chen, X., Feng, S., Song, Y., and Liang, L. (2022). Chemical Stability of Ascorbic Acid Integrated into Commercial Products: A Review on Bioactivity and Delivery Technology. Antioxidants, 11.","DOI":"10.3390\/antiox11010153"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5078","DOI":"10.1021\/jf9805404","article-title":"Degradation of Ascorbic Acid in Aqueous Solution","volume":"46","author":"Yuan","year":"1998","journal-title":"J. Agric. Food Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1021\/bm070309b","article-title":"Degradation of High-Molar-Mass Hyaluronan and Characterization of Fragments","volume":"8","author":"Kogan","year":"2007","journal-title":"Biomacromolecules"}],"container-title":["Applied Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3417\/16\/3\/1491\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:19:18Z","timestamp":1770034758000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3417\/16\/3\/1491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["app16031491"],"URL":"https:\/\/doi.org\/10.3390\/app16031491","relation":{},"ISSN":["2076-3417"],"issn-type":[{"value":"2076-3417","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,2]]}}}