In-vitro and clinical evaluation of an oral mucosal adhesive film containing indomethacin.
To develop a new mucoadhesive film containing an analgesic combining clinical efficacy and patient comfort, we prepared and evaluated a two-layered film consisting of an adhesive layer containing indomethacin (IM) as the active ingredient and carboxyvinyl polymer (CP) as a bonding agent and a nonadhesive layer containing polyethylene glycol (PEG) to improve film texture. In in vitro and in vivo adhesive tests, the optimal concentration of CP that could be applied to the mucous membrane was 0.2% or 0.3%. Stability testing determined that the optimal storage conditions and expiration period were 4 degrees C without shade and 4 weeks, respectively. The film was clinically evaluated in patients with oral pain. IM at concentrations of 0.5% and 1% provided optimum analgesic effects, and the effects were the greatest in the 1% IM group. The addition of PEG to the nonadhesive layer reduced the number of patients experiencing discomfort at the site where the film was applied. Therefore this film formulation may be useful for local analgesic application due to its low dose requirement, moderate adhesion, and comfortable texture.
Takeuchi
Kazuyo
K
Division of Medical and Pharmaceutical Sciences-II, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara City, Japan.
Watanabe
Machiko
M
Yanagi
Mashiho
M
Murakami
Isao
I
Hosono
Hiroyuki
H
Nishizawa
Satoru
S
Chigono
Yoshiho
Y
Hirabayashi
Shinichi
S
Matsuda
Juzo
J
Yamaoka
Keiko
K
Inoue
Keizo
K
D000268:Adhesiveness; D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects; D002482:Cellulose / Q000031:analogs & derivatives; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004355:Drug Stability; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage* / Q000009:adverse effects; D009061:Mouth Mucosa; D010146:Pain / Q000188:drug therapy*; D011092:Polyethylene Glycols; D012995:Solubility; D016896:Treatment Outcome
D000700:Analgesics; D004304:Dosage Forms; D011092:Polyethylene Glycols; D002482:Cellulose; C008079:hydroxypropylcellulose; D007213:Indomethacin