Design and in vivo evaluation of a patch system based on thiolated polymers.
A new oral patch delivery system has been designed to increase the overall oral bioavailability of drugs within the gastrointestinal tract. The patch system consists of four layered films: a mucoadhesive matrix layer, a water insoluble backing layer, a middle layer and an enteric surface layer. The separation layer between the two matrix layers contained lactose, starch and confectioners' sugar. The matrix layer, exhibiting a diameter of 2.5 mm and a weight of 5 mg, comprised Polycarbophil-cysteine conjugate (49%), fluoresceine isothiocyanate-dextran (26%), glutathione (5%), and mannitol (20%). A standard tablet formulation consisting of the same matrix served as control. Entire fluoresceine isothiocyanate-dextran (FD(4)) was released from the delivery system within 2 h. For in vivo studies patch systems were administered orally to male Sprague-Dawley rats. Maximum FD(4) concentration in blood of the patch system was 46.1 +/- 8.9 ng/mL and was reached 3 h after administration. In contrast c(max) of control tablets displayed 50.5 +/- 14.9 ng/mL after 2 h and the absorption of FD(4) after administration in oral solution was negligible. The absolute bioavailability of orally administered patch systems and control tablets was 0.54% and 0.32% respectively. Results of this study indicate that a prolonged and higher oral bioavailability of FD(4) is obtained with patches than with tablets.
Hoyer
Herbert
H
Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innsbruck, Austria.
Greindl
Melanie
M
Bernkop-Schnürch
Andreas
A
D000180:Acrylic Resins / Q000737:chemistry* / Q000378:metabolism; D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003545:Cysteine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D003692:Delayed-Action Preparations; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004304:Dosage Forms; D004337:Drug Carriers; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013552:Swine; D013607:Tablets
D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D003911:Dextrans; D004304:Dosage Forms; D004337:Drug Carriers; D005079:Excipients; D013607:Tablets; C015219:fluorescein isothiocyanate dextran; C030312:calcium polycarbophil; D016650:Fluorescein-5-isothiocyanate; D003545:Cysteine