In vitro and in vivo characteristics of prochlorperazine oral disintegrating film.
Oral disintegrating film containing prochlorperazine, a dopamine D(2) receptor antagonist with anti-emetic property, was newly developed using microcrystalline cellulose, polyethlene glycol and hydroxypropylmethyl cellulose as the base materials. The uniformity of dosage units of the preparation was acceptable according to the criteria of JP15 or USP27. The film showed an excellent stability at least for 8 weeks when stored at 40 degrees C and 75% in humidity. The dissolution test revealed a rapid disintegration property, in which most of prochlorperazine dissolved within 2 min after insertion into the medium. Subsequently, rats were used to compare pharmacokinetic properties of the film preparation applied topically into the oral cavity with those of oral administration of prochlorperazine solution. None of the parameters, including T(max), C(max), area under curves, clearance and steady-state distribution volume was significantly different between oral disintegrating film and oral solution. These findings suggest that the present prochlorperazine-containing oral film is potentially useful to control emesis induced by anti-cancer agents or opioid analgesics in patients who limit the oral intake.
Nishimura
Misao
M
Tsukioka Co., Ltd., Kagamihara, Gifu, Japan.
Matsuura
Katsuhiko
K
Tsukioka
Tadao
T
Yamashita
Hirotaka
H
Inagaki
Naoki
N
Sugiyama
Tadashi
T
Itoh
Yoshinori
Y
D000278:Administration, Buccal; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004304:Dosage Forms; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D065347:Hypromellose Derivatives; D008297:Male; D013058:Mass Spectrometry; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011346:Prochlorperazine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013997:Time Factors
D000932:Antiemetics; D004304:Dosage Forms; D005079:Excipients; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D002482:Cellulose; D008747:Methylcellulose; C109691:microcrystalline cellulose; D011346:Prochlorperazine