Effects of the Mucoadhesive Polymer Polycarbophil on the Intestinal Absorption of a Peptide Drug in the Rat

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 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.

Biopolymer Mucoadhesives

“…Table 3 also shows the potential of the mussel foot glue protein (Schnurrer and Lehr, 1996). Lehr et al (1992a) and Schnurrer and Lehr (1996) also obtained the rather surprising result of a very favourable interaction for the synthetic polyanionic polymer, polycarbophil. We will consider these results again later when we have dealt with the molecular hydrodynamics.…”

Liposome-Based Mucoadhesive Formulations for Oral Delivery of Macromolecules

“…Longer and colleagues (Longer et al 1985) first showed that delayed GI transit induced by bioadhesive polymers could lead to increased oral bioavailability of a drug. Other researchers have prepared a multiunit bioadhesive system by coating microspheres of poly-hydroxyethyl-methacrylate with mucoadhesive polymers using laboratory-scale equipment (Lehr et al 1990(Lehr et al , 1992. Akiyama and coworkers (Akiyama et al 1995) prepared a polyglycerol ester of fatty acid-based microspheres coated with Carbopol934P (CP) and CP-dispersing microspheres to evaluate their mucoadhesive properties.…”

Prolonged Intestinal Absorption of Cephradine with Chitosan-Coated Ethylcellulose Microparticles in Rats.

“…Mucoadhesive polymers are available for localization or slow transit of microparticles at the gastrointestinal tract. 7,[9][10][11][12][13][14] In this study, ethylcellulose was used to prepare microparticles showing prolonged release of cephradine, and chitosan was applied to give the microparticles mucoadhesive characteristics.…”

“…1,[6][7][8] Further, their gastrointestinal transit can be modified with mucoadhesive polymers. [9][10][11] When the mucoadhesive polymers interact with mucous membranes of the GI tract, they are considered to be localized or trapped at the adhesive sites, which may result in prolonged duration of absorption. 7,[12][13][14] Chitosan is adhesive to the intestinal mucosa, and chitosan enhances drug absorption from microparticulate dosage forms.…”