Semi-solid dosage form of clonazepam for rapid oral mucosal absorption.
BACKGROUND
In order to obtain an alternative to the intravenous (i.v.) dosage form of clonazepam (CZ), an oral droplet formulation of CZ was developed previously; however, the droplet was physically unstable. Therefore, in the present study, it was attempted to develop an easily-handled dosage form, which was more physically stable and allowed rapid drug absorption from oral mucosa.


METHODS
A semi-solid dosage form, composed of polyethylene glycol 1500 (PEG), CZ, and oleic acid (OA) at 37/1/2 (w/w) and named PEG/CZ/OA, and a semi-solid dosage form containing PEG and CZ at 39/1 (w/w), called PEG/CZ, were prepared. Their physical stability in air at room temperature and oral mucosal absorption in rats were investigated.


RESULTS
The semi-solid dosage forms were much more stable physically than the droplet, that is, no recrystallization of CZ was observed for at least 8 days. The effective concentration for humans and rats (20 ng/mL or more) was achieved within 30 min after buccal administration for both PEG/CZ/OA and PEG/CZ. The plasma concentration increased gradually and less varied at each time point for PEG/CZ/OA. PEG/CZ/OA was found to show more rapid and higher absorption of CZ in buccal administration than in sublingual administration.


CONCLUSIONS
Buccal administration with the semi-solid dosage PEG/CZ with or without OA was suggested to be a possibly useful novel dosage form as an alternative to i.v. injection.
Department of Drug Delivery Research, Hoshi University, Ebara, Shinagawa-ku, Tokyo, Japan.
Osamu
O
Sakata
Yoshiharu
Y
Machida
Hiraku
H
Onishi
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics; D002998:Clonazepam / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004304:Dosage Forms; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D008297:Male; D009061:Mouth Mucosa / Q000378:metabolism*; D019301:Oleic Acid / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D004304:Dosage Forms; D019301:Oleic Acid; D011092:Polyethylene Glycols; D002998:Clonazepam