title: Transbuccal delivery of doxepin: studies on permeation and histological investigation.
abstract: According to previous studies reporting the anesthetic/analgesic action of oral topical doxepin administration, this study evaluated a model of buccal permeation to determine the depth of delivery of doxepin into excised porcine buccal mucosa following topical application of a saturated aqueous doxepin solution. Buccal mucosa permeation studies were performed using Franz diffusion cells. Cumulative amounts of doxepin permeated were plotted as a function of time. Kinetic permeation parameters as flux (Js), lag time (Tl) and permeability coefficient (Kp) were calculated. Theoretical human plasmatic steady-state doxepin concentration and drug retained in the tissue were also determined in order to evaluate its potential therapeutic use, central or peripheral. Finally, a histological evaluation of the buccal mucosa was performed to test potential damage due to the permeation phenomenon. Obtained results showed a poor aqueous doxepin permeation through buccal mucosa membrane (median parameters Js=34.79 μg/h, Kp=0.49×10(-3)cm/h and Tl=2.8h). Predicted doxepin plasma concentrations would reach 46 ng/mL, far from the required to have central nervous system activity as tricyclic agent. However, median doxepin amount remaining in the mucosa membrane was 0.24 μg/cm(2)/μg tissue, which evidenced a reservoir function of the buccal mucosa. Histologically, no structural damage was observed in the tissues. This study lays the foundation for further research within this area with a view to potentially adopting alternative strategies for enhanced buccal absorption of doxepin in clinical practice.
authors.affiliation: Animal Facility, Bellvitge Health Sciences Campus, University of Barcelona, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Gimeno
authors.affiliation: Biopharmaceutical and Pharmacokinetics Unit, School of Pharmacy, University of Barcelona, Spain.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Calpena
authors.affiliation: Biopharmaceutical and Pharmacokinetics Unit, School of Pharmacy, University of Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Sanz
authors.affiliation: Biopharmaceutical and Pharmacokinetics Unit, School of Pharmacy, University of Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Mallandrich
authors.affiliation: Biopharmaceutical and Pharmacokinetics Unit, School of Pharmacy, University of Barcelona, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Peraire
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, School of Pharmacy, University of Granada, Spain. Electronic address: beatrizclares@ugr.es.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Clares
mesh_terms: D000278:Administration, Buccal; D000700:Analgesics / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D004316:Doxepin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D066298:In Vitro Techniques; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D065568:Oral Mucosal Absorption / Q000187:drug effects; D010539:Permeability; D011237:Predictive Value of Tests; D013552:Swine; D014018:Tissue Distribution
chemical_list: D000700:Analgesics; D004316:Doxepin
keywords: Buccal delivery; Doxepin; Ex vivo drug permeation; Pain; Porcine buccal mucosa; PubChem CID 6419921