Preparation of a fast dissolving oral thin film containing dexamethasone: a possible application to antiemesis during cancer chemotherapy.
We prepared fast dissolving oral thin film that contains dexamethasone and base materials, including microcrystalline cellulose, polyethylene glycol, hydroxypropylmethyl cellulose, polysorbate 80 and low-substituted hydroxypropyl cellulose. This preparation showed excellent uniformity and stability, when stored at 40 degrees C and 75% in humidity for up to 24 weeks. The film was disintegrated within 15s after immersion into distilled water. The dissolution test showed that approximately 90% of dexamethasone was dissolved within 5 min. Subsequently, pharmacokinetic properties of dexamethasone were compared in rats with oral administration of 4 mg dexamethasone suspension or topical application of the film preparation containing 4 mg dexamethasone to the oral cavity. Pharmacokinetic parameters were similar between the two groups in which C(max) (h), T(max) (microg/mL), AUC (microg/mL/h) and half-life (h) were 12.7+/-6.6 (mean+/-SD, N=10), 3.4+/-1.4, 93.6+/-37.8 and 1.66+/-0.07, respectively, for oral suspension and 13.3+/-4.0, 3.2+/-1.0, 98.0+/-22.3 and 1.65+/-0.06, respectively, for film preparation. These findings suggest that the fast dissolving oral thin film containing dexamethasone is likely to become one of choices of dexamethasone preparations for antiemesis during cancer chemotherapy.
Shimoda
Hiroyoshi
H
Department of Pharmacy, Gifu University Hospital, Gifu, Japan.
Taniguchi
Kazumi
K
Nishimura
Misao
M
Matsuura
Katsuhiko
K
Tsukioka
Tadao
T
Yamashita
Hirotaka
H
Inagaki
Naoki
N
Hirano
Kazuyuki
K
Yamamoto
Mayumi
M
Kinosada
Yasutomi
Y
Itoh
Yoshinori
Y
D000284:Administration, Oral; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D006207:Half-Life; D008297:Male; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
D000932:Antiemetics; D000970:Antineoplastic Agents; D004337:Drug Carriers; D005079:Excipients; D003907:Dexamethasone