{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:01:26Z","timestamp":1787029286396,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"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>The mouth can be affected by important inflammatory processes resulting from localized or systemic diseases such as diabetes, AIDS and leukemia, among others, and are manifested in various types of buccal sores typically presenting pain. This work focuses on the design, formulation, and characterization of four semisolid formulations for oral mucosa in order to symptomatically treat these painful processes. The formulations have two active pharmaceutical ingredients, triamcinolone acetonide (TA) and lidocaine hydrochloride (LIDO). The formula also contains, as an excipient, Orabase\u00ae, which is a protective, hydrophobic, and anhydrous adhesive vehicle, used to retain or facilitate the application of active pharmaceutical ingredients to the oral mucosa. After designing the formulations, an analytical method for TA was validated using HPLC so as to achieve reliable analytical results. Franz-type diffusion cells were used to perform drug release studies using synthetic membrane, and permeation studies using buccal mucosa, estimating the amount and rate of TA permeated across the tissue. Additionally, sublingual permeation studies were carried out to evaluate a scenario of a continuous contact of the tongue with the applied formulation. Permeation fluxes and the amount of TA retained within sublingual mucosa were similar to those in buccal mucosa, also implying anti-inflammatory activity in the part of the tongue that is in direct contact with the formulation. In addition, the dynamic conditions of the mouth were recreated in terms of the presence of phosphate buffered saline, constant movement of the tongue, pH, and temperature, using dissolution equipment. The amount of TA released into the phosphate buffered saline in dynamic conditions (subject to being ingested) is well below the normal oral doses of TA, for which the formulation can be considered safe. The formulations applied to buccal or sublingual mucosas under dynamic conditions permit the successful retention of TA within either tissue, where it exerts anti-inflammatory activity. The four formulations studied show a pseudoplastic and thixotropic behavior, ideal for topical application. These results evidence the potential of these topical formulations in the treatment of inflammatory processes in the buccal mucosa.<\/jats:p>","DOI":"10.3390\/pharmaceutics13071080","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T09:32:07Z","timestamp":1626341527000},"page":"1080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Biopharmaceutical Study of Triamcinolone Acetonide Semisolid Formulations for Sublingual and Buccal Administration"],"prefix":"10.3390","volume":"13","author":[{"given":"Marta","family":"M\u00e1rquez Valls","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Av. Joan XXIII 29-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Mart\u00ednez Labrador","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Av. Joan XXIII 29-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6080-5340","authenticated-orcid":false,"given":"Lyda","family":"Halbaut Bellowa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Av. Joan XXIII 29-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dom\u00e9nica","family":"Bravo Torres","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Av. Joan XXIII 29-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9178-635X","authenticated-orcid":false,"given":"Paulo C.","family":"Granda","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Av. Joan XXIII 29-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Mi\u00f1arro Carmona","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Av. Joan XXIII 29-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8556-5531","authenticated-orcid":false,"given":"David","family":"Lim\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Av. Joan XXIII 29-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-4821","authenticated-orcid":false,"given":"Ana C.","family":"Calpena Campmany","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Av. Joan XXIII 29-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"ref_1","first-page":"80","article-title":"Tratamiento de las enfermedades de la cavidad bucal","volume":"22","year":"2003","journal-title":"OFFARM"},{"key":"ref_2","unstructured":"National Center for Biotechnology Information (2019, September 14). PubChem Database. Triamcinolone Acetonide, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/6436#section=Pharmacology-and-Biochemistry."},{"key":"ref_3","first-page":"499","article-title":"Oral Ulcers: Differential Diagnosis and Treatment","volume":"145","year":"2015","journal-title":"Med. Cl\u00edn. (Engl. Ed.)"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.oooo.2019.07.024","article-title":"Intralesional Triamcinolone Acetonide Therapy for Inflammatory Oral Ulcers","volume":"128","author":"Fantozzi","year":"2019","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1002\/lary.5541040511","article-title":"Treatment of Aphthous Ulcers in AIDS Patients","volume":"104","author":"Friedman","year":"1994","journal-title":"Laringoscope"},{"key":"ref_6","first-page":"279","article-title":"Biological In Vitro Models for Absorption by Nonoral Routes","volume":"5","author":"Colombo","year":"2007","journal-title":"Compr. Med. Chem. II"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jconrel.2011.01.027","article-title":"Advances in Oral Transmucosal Drug Delivery","volume":"153","author":"Patel","year":"2011","journal-title":"J. Control Release"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Valls, M.M., Labrador, A.M., Bellowa, L.H., Torres, D.B., Granda, P.C.S., Lim\u00f3n, D., and Calpena-Campmany, A. (2021). Galenic and Biopharmaceutical Study of the Triamcinolone Acetonide and Lidocaine Hydrochloride Semi-solid Formulations for Buccal Administration. Proceedings, 78.","DOI":"10.3390\/IECP2020-08681"},{"key":"ref_9","unstructured":"Acofarma (2019, September 17). Fichas de Informaci\u00f3n T\u00e9cnica: Excipiente Acofar Adhesivo Oral. Available online: https:\/\/formulasmagistrales.acofarma.com\/idb\/descarga\/3\/f9b97fcbceaef2bf.pdf."},{"key":"ref_10","first-page":"860","article-title":"Evaluation of different preparation methods for a preservative free triamcinolone acetonide preparation for intravitreal administration: A validated stability indicating HPLC-method","volume":"65","author":"Korodi","year":"2010","journal-title":"Pharmazie Int. J. Pharm. Sci."},{"key":"ref_11","unstructured":"ISO: International Organization for Standardization (1994). Guide 8402: Quality Vocabulary, ISO."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Huber, L. (2007). Validation and Qualification in Analytical Laboratories, Informa Healthcare. [2nd ed.].","DOI":"10.3109\/9780849382680"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.jpba.2005.09.018","article-title":"Simultaneous determination of triamcinolone acetonide and oxymetazoline hydro-chloride in nasal spray formulations by HPLC","volume":"40","author":"Sudsakorn","year":"2006","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.jpba.2018.07.015","article-title":"Pranoprofen quantification in ex vivo corneal and scleral permeation samples: Analytical validation","volume":"160","author":"Abrego","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_15","unstructured":"EMA: European Medicines Agency (2019, September 20). Guideline on Bionalytical Method Validation, Available online: http:\/\/www.ema.europa.eu\/docs\/enGB\/documentlibrary\/Scientificguideline\/2011\/08\/WC500109686.pdf."},{"key":"ref_16","unstructured":"AEFI: Asociaci\u00f3n Espa\u00f1ola de Farmac\u00e9uticos de la Ind\u00fastria (2001). Validaci\u00f3n de M\u00e9todos Anal\u00edticos, AEFI."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Segura, L., Parra, A., Calpena, A.C., Gimeno, \u00c1., and Boix-Monta\u00f1es, A. (2020). Carprofen Permeation Test through Porcine Ex Vivo Mucous Membranes and Ophthalmic Tissues for Tolerability Assessments: Validation and Histological Study. Vet. Sci., 7, Available online: https:\/\/www.mdpi.com\/2306-7381\/7\/4\/152\/htm.","DOI":"10.3390\/vetsci7040152"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1467-2494.2004.00247.x","article-title":"The characterization of the semisolid W\/O\/W emulsions with low concentrations of the primary polymeric emulsifier","volume":"27","author":"Vasiljevic","year":"2005","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Rapp, B.E. (2017). Microfluidics: Modeling, Mechanics and Mathematics, Elsevier. [1st ed.].","DOI":"10.1016\/B978-1-4557-3141-1.50009-5"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15744","DOI":"10.1039\/c3ra43070g","article-title":"Studies on the structure-property relationship of sodium alginate based thixotropic hydrogels","volume":"3","author":"Chejara","year":"2013","journal-title":"RSC Adv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5901","DOI":"10.3390\/md13095901","article-title":"Physical stability studies of semisolid formulations from natural compounds loaded with chitosan microspheres","volume":"13","author":"Acosta","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ijpharm.2017.11.027","article-title":"Development of a mucoadhesive delivery system for control release of doxepin with application in vaginal pain relief associated with gynecological surgery","volume":"535","author":"Sanz","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1177\/00912700022009134","article-title":"A Study Comparing the Clinical Pharmacokinetics, Pharmacodynamics, and Tolerability of Triamcinolone Acetonide Budesonide DryPowder Inhaler following Inhalation Administration","volume":"40","author":"Argenti","year":"2000","journal-title":"J. Clin. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2005.01.024","article-title":"Buccal penetration enhancers--how do they really work?","volume":"105","author":"Nicolazzo","year":"2005","journal-title":"J. Control Release"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nrd1304","article-title":"Current status and future potential of transdermal drug delivery","volume":"3","author":"Prausnitz","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0378-5173(94)90098-1","article-title":"Effect of d-limonene on transdermal permeation of nifedipine and domperidone","volume":"103","author":"Calpena","year":"1994","journal-title":"Int. J. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1517\/14740338.2016.1140743","article-title":"Long-term side effects of glucocorticoids","volume":"15","author":"Oray","year":"2016","journal-title":"Expert. Opin. Drug Saf."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/7\/1080\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:30:52Z","timestamp":1760164252000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/7\/1080"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,15]]},"references-count":27,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["pharmaceutics13071080"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13071080","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,15]]}}}