Design and in vivo evaluation of a patch system based on thiolated polymers

J Pharm Sci. 2009 Feb;98(2):620-7. doi: 10.1002/jps.21480.

Abstract

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.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Acrylic Resins / chemistry*
  • Acrylic Resins / metabolism
  • Adhesiveness
  • Administration, Oral
  • Animals
  • Biological Availability
  • Chemistry, Pharmaceutical
  • Cysteine / analogs & derivatives
  • Cysteine / chemistry*
  • Cysteine / metabolism
  • Delayed-Action Preparations
  • Dextrans / administration & dosage
  • Dextrans / chemistry
  • Dextrans / pharmacokinetics
  • Dosage Forms
  • Drug Carriers*
  • Drug Compounding
  • Excipients / chemistry
  • Fluorescein-5-isothiocyanate / administration & dosage
  • Fluorescein-5-isothiocyanate / analogs & derivatives
  • Fluorescein-5-isothiocyanate / chemistry
  • Fluorescein-5-isothiocyanate / pharmacokinetics
  • Injections, Intravenous
  • Intestinal Mucosa / metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Solubility
  • Swine
  • Tablets

Substances

  • Acrylic Resins
  • Delayed-Action Preparations
  • Dextrans
  • Dosage Forms
  • Drug Carriers
  • Excipients
  • Tablets
  • fluorescein isothiocyanate dextran
  • calcium polycarbophil
  • Fluorescein-5-isothiocyanate
  • Cysteine