title: Controlled indomethacin release from mucoadhesive film: in vitro and clinical evaluations.
abstract: To develop a film formulation allowing controlled release for long-term analgesia, we selected ethyl cellulose (EC) as a novel additive, prepared a film formulation using indomethacin (IM film), and evaluated it in vitro and clinically. In the in vitro experiments, the effects of the EC concentration on the release rate of IM and on the adhesion force to the mucous membrane were investigated. The addition of 10% EC resulted in more sustained slow release compared with no EC, and the adhesion of the film with 10% EC added was similar to that of films containing carboxyvinyl polymer, which we reported previously showed significantly increased adhesion. A two-layered film consisting of an adhesive layer with 2% or 1% IM and 10% EC and a nonadhesive layer with 2% polyethylene glycol as a softening agent, was investigated for clinical use. Film consisting of an adhesive layer with 2% IM and 10% EC exhibited rapid onset of potent analgesia and was expected to prolong the duration of analgesia. These results suggest that IM film with EC added may be useful clinically, since it shows both immediate analgesic effects and prolonged duration of release.
authors.affiliation: Division of Medical and Pharmaceutical Sciences-II, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Sagamihara City, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanabe
authors.forename: Machiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Mashiho
authors.initials: M
authors.lastname: Yanagi
authors.forename: Satoru
authors.initials: S
authors.lastname: Nishizawa
authors.forename: Yoshiho
authors.initials: Y
authors.lastname: Chigono
authors.forename: Juzo
authors.initials: J
authors.lastname: Matsuda
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamaoka
authors.forename: Keizo
authors.initials: K
authors.lastname: Inoue
mesh_terms: D000268:Adhesiveness; D000277:Adjuvants, Pharmaceutic; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002482:Cellulose / Q000031:analogs & derivatives*; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D004355:Drug Stability; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa; D010146:Pain / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000277:Adjuvants, Pharmaceutic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004304:Dosage Forms; C013517:ethyl cellulose; D002482:Cellulose; D007213:Indomethacin