Novel mucoadhesive oral patch containing diazepam.
The oral patch of diazepam (DZ) was developed to achieve a rapid absorption of DZ for the emergency treatment of epileptic seizure or anxiety disorder. The patch was composed of the outer mucoadhesive Carbopol 934 region, central drug region, and Tegaderm backing film. DZ (3 mg) was dissolved in propylene glycol (PG) alone or PG containing oleic acid (OA) at 5.6% (w/w), and used as the drug region. The patches with and without OA were attached to the mucosa of cheek in rats. The patch with OA exhibited the plasma level of more than 200 ng/mL at 10 min after administration, then the plasma concentration decreased gradually. The patch without OA displayed a plasma level of less than 30 ng/mL during 40 min after administration. To the contrary, in the in vitro drug permeation using a cellulose membrane, the patch without OA showed a three times faster permeation rate than the patch with OA, suggesting that the direct action of OA to mucosa might be associated with absorption enhancement. It was demonstrated that the patch with OA showed a good adhesion to oral mucosa and worked efficiently for rapid absorption of DZ.
Onishi
Hiraku
H
Department of Drug Delivery Research, Hoshi University, Tokyo, Japan. onishi@hoshi.ac.jp
Sakata
Osamu
O
Masuda
Kosuke
K
Machida
Yoshiharu
Y
D000042:Absorption / Q000187:drug effects; D000179:Acrylates / Q000737:chemistry; D000268:Adhesiveness; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D002482:Cellulose; D002610:Cheek; D003975:Diazepam / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D008297:Male; D008567:Membranes, Artificial; D009061:Mouth Mucosa / Q000378:metabolism*; D019301:Oleic Acid / Q000494:pharmacology*; D019946:Propylene Glycol / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D000179:Acrylates; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D008567:Membranes, Artificial; D019301:Oleic Acid; D019946:Propylene Glycol; D002482:Cellulose; C453622:carbopol 934P; D003975:Diazepam