The long-term release of antibiotics from monolithic nonporous polymer implants for use as tympanostomy tubes

A technology is elaborated for the fabrication of a novel tympanostomy tube (IT) from solidified polymer melts (Elvax and polyurethane) and antibiotics (ciprofloxacin and (+)- usnic acid) for insertion into the tympanic membrane (ear drum) according to the established surgical procedure. The long-term in vitro release kinetics of the antibiotics into liquid water was assessed using standard methods. The measured kinetic curves revealed two stages of antibiotic release into finite space. During the first stage (fast), the release rate was almost invariant and was determined by diffusion through the steady diffusion layer formed due to solution agitation. In this first stage, the influence of the initial internal transport was weak because it takes place at a negligibly small distance from the interface, and therefore, at a negligible concentration drop. After the antibiotic concentration decreased within the much broader layer of the matrix near the interface, internal transport became important. This manifested itself as the second stage in the measured kinetics of release curves. which were characterized by a gradual decrease in rate. The minimum inhibition concentrations of three antibiotics/antimicrobial compounds for four bacterial species were measured. The first stage of fast release from the polymer implant lasted 6 days at it polymer loading by ciprofloxacin (0.03 g/cm(3)), and this was sufficient to prevent biofilm formation on the surface of the implant material. The measured kinetic curves of drug release showed a more rapid decrease in the release rate compared to the Higuchi approximation. Comparison with existing theories, which account for the finite rate of drug dissolution, showed that this may explain the observed deviation from the diffusion-controlled Higuchi model. Large dimensions of drug particles and their aggregation retarded the dissolution stage, and consequently, the release rate. Melt blending was found to cause drug particle aggregation within the polymer matrices, which was confirmed by microscopic reexamination of the polymer implant materials. (C) 2009 Elsevier B.V. All rights reserved.