1. Development of a buccal doxepin platform for pain in oral mucositis derived from head and neck cancer treatment.
- Author
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Sanz R, Calpena AC, Mallandrich M, Gimeno Á, Halbaut L, and Clares B
- Subjects
- Animals, Doxepin administration & dosage, Doxepin chemistry, Female, Head and Neck Neoplasms drug therapy, Histamine Antagonists administration & dosage, Histamine Antagonists chemistry, Histamine Antagonists metabolism, Male, Mouth Mucosa drug effects, Mouthwashes administration & dosage, Mouthwashes chemistry, Organ Culture Techniques, Pain drug therapy, Stomatitis drug therapy, Swine, Treatment Outcome, Doxepin metabolism, Head and Neck Neoplasms metabolism, Mouth Mucosa metabolism, Mouthwashes metabolism, Pain metabolism, Stomatitis metabolism
- Abstract
This study describes the development of semisolid formulations containing doxepin (DOX) for pain relief in oral mucositis, frequently related to chemotherapy and/or radiotherapy treatments in patients with head and neck cancer. Chemical permeation enhancers were evaluated and selected according to the results obtained from rheological studies, drug release, and drug permeation and retention through buccal mucosa. Finally, the selected formulation was compared in vivo, with a reference DOX mouthwash, whose clinical efficacy had been previously reported. The obtained findings showed that an orabase® platform loading transcutol® (10%) and menthol (5%) for the buccal vehiculization of DOX exhibited a decreased elastic and viscous behavior improving its application. The main drug release mechanism could be considered as diffusion according to Higuchi model. Obtained DOX permeation rates were considered optimal for an analgesic effect and far below to an antidepressant activity. Similar in vivo plasma concentrations were found for the semisolid formulation and the reference mouthwash. However, DOX amounts retained in the mucosa of animals for the semisolid formulation were higher than the reference, which let us hypostatize even stronger potential local therapeutic effect with additional advantages such as, mucoadhesive properties, absence of alcohol, some degree of freshness, as well as, drug palatability improvement., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
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