Controlled release of levamisole from poly-(epsilon-caprolactone) matrices .2. Effects of water-soluble polymer and iron powder incorporated into the matrices

Mixtures of hydrophobic-polymer/hydrophilic-polymer and hydrophobic-polymer/hydrophilic-polymer/iron powder were evaluated for the construction of rumino-reticulum devices (RRDs) containing levamisole hydrochloride as anthelmintic agent. A faster release profile of levamisole was achieved by incorporating a hydrophilic polymer such as polyethylene glycol 6000 and/or iron powder into a hydrophobic polymer such as poly-(epsilon-caprolactone) constituting the biodegradable matrix. In this hydrophobic/hydrophilic polymeric system, poly-(epsilon-caprolactone) maintained the integrity of the matrix, whereas polyethylene glycol 6000 dissolved from the matrix as the drug was released. Thus, the area-to-volume ratio of the device remained constant over the duration of the drug release. In vitro drug release studies were conducted at an ionic strength and pH as near as possible to those encountered in the rumen of cattle which generally varies from about 5.5 to 7.0. Drug release rates decreased as the matrix system:drug ratio increased. The drug release kinetics from these RRDs exhibit linearity with t(1/2) when the matrix was constituted with poly-(epsilon-caprolactone) and the release of the drug was determined as resulting from a diffusional mechanism following Higuchi's equation. When a part of the hydrophobic matrix was replaced with polyethylene glycol 6000 (5-15%), no linear correlation was observed with t(1/2) and the faster release of the drug was associated with the dissolution of the polyethylene glycol 6000. Complete dissolution of the drug at the typical pH encountered in the rumenal fluids and 39 degrees C would ensure good bioavailability of the drug following oral administration.