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Design, development and characterization of buccal bioadhesive films of Doxepin for treatment of odontalgia.

Abstract
Tricyclic antidepressants, as doxepin hydrochloride (DH), may have analgesic local effect due to its biochemical mechanism of action. Delivery of DH directly to the oral cavity could be an interesting alternative for toothache due to its analgesic local effect. One problem associated with the mucosal administration routes is the short residence time of the dosage form on the mucosal membranes. In this sense, we have developed new doxepin mucoadhesive films able of reducing pain and increasing the effectiveness of treatment. For this purpose, we tested three different polymers: chitosan, sodium hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (SCMC) in film elaboration. The results obtained show that all films are hydrophilic matrices that absorb water when placed in an aqueous media. All the films hydrated very quickly, reaching high percentage of swelling after just few minutes (5 min for SCMC, 2 min for HPMC and 30 min for chitosan). Moreover, the SCMC and HPMC films were dissolved whereas chitosan was not dissolved. Dissolution also leads to viscous liquids with a higher retention time over mucosal surfaces what may lead to adhesive interactions. In vitro permeation studies showed that for all the formulations studied, SCMC (19.91%), HPMC (69.5%) and chitosan (24.17%), the percentage of drug permeated increased compared to the drug solution (8.26%). Specifically the HPMC film presents greater amounts of doxepin permeated (49.27 ± 4.47 µg/cm(2)).
AuthorsH Castán, M A Ruiz, B Clares, M E Morales
JournalDrug delivery (Drug Deliv) Vol. 22 Issue 6 Pg. 869-76 ( 2015) ISSN: 1521-0464 [Electronic] England
PMID24670096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antidepressive Agents, Tricyclic
  • Doxepin
  • Hypromellose Derivatives
  • Chitosan
  • Carboxymethylcellulose Sodium
Topics
  • Adhesiveness
  • Administration, Buccal
  • Antidepressive Agents, Tricyclic (administration & dosage)
  • Calorimetry, Differential Scanning
  • Carboxymethylcellulose Sodium (chemistry)
  • Chemistry, Pharmaceutical
  • Chitosan (chemistry)
  • Doxepin (administration & dosage)
  • Drug Liberation
  • Hydrogen-Ion Concentration
  • Hypromellose Derivatives (chemistry)
  • Toothache (drug therapy)

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