Affiliation:
1. Center for Bio-Pharmaceutical Sciences, Leiden University, The Netherlands
2. Department of Pharmaceutics, Faculty of Pharmacy, Utrecht University, The Netherlands
Abstract
Abstract
The absorption across rat intestinal tissue of the model peptide drug 9-desglycinamide, 8-arginine vasopressin from bioadhesive formulations was studied in-vitro, in a chronically isolated internal loop in-situ and after intraduodenal administration in-vivo. A controlled-release bioadhesive drug delivery system was tested, consisting of microspheres of poly(2-hydroxyethyl methacrylate) with a mucoadhesive Polycarbophil-coating, as well as a fast-release formulation consisting of an aqueous solution of the peptide in a suspension of Polycarbophil particles. Using the controlled-release system, a slight improvement of peptide absorption was found in-vitro in comparison with a non-adhesive control system, but not in-situ or in-vivo. In contrast, bioavailability was significantly increased in all three models from the Polycarbophil suspension in comparison with a solution of the drug in saline. The effect appeared to be dose-dependent, indicative of intrinsic penetration-enhancing properties of the mucoadhesive polymer. A prolongation of the absorption phase in-vitro and in the chronically isolated loop in-situ suggested that the polymer was able to protect the peptide from proteolytic degradation. This could be confirmed by degradation studies in-vitro. The duration of the penetration enhancing/enzyme inhibiting effect was diminished with increasing complexity of the test model, in the same way as was previously found for the bioadhesive effect. This interrelationship suggests that the observed improvement in peptide absorption and the mucoadhesive properties of this polymer are associated. The development of a fast-release oral dosage form for peptide drugs on the basis of Polycarbophil appears to be possible.
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
Reference12 articles.
1. Site specific intestinal absorption using bioadhesives: improved oral delivery of peptide drugs by means of bioadhesive polymers;Junginger,1990
2. Enzymatic barriers to peptide and protein absorption;Lee;CRC Crit. Rev. Ther. Drug Carrier Syst.,1988
3. Intestinal transit of bioadhesive microspheres in an in situ loop in the rat—a comparative study with copolymers and blends based on poly(acrylic acid);Lehr;J. Control. Rel.,1990
4. Release of a peptide drug from microspheres of poly(2-hydroxyethyl-methacrylate) relevant for the development of an oral bioadhesive drug delivery system;Lehr;Eur. J. Pharm. Biopharm.,1992
5. The role of mucus for the concept of mucoadhesion in controlling gastrointestinal transit of drug delivery systems;Lehr;J. Pharm. Sci.,1992
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