Compression molding of biodegradable drug-eluting implants for sustained release of metronidazole and doxycycline

The purpose of this report was to develop solvent-free biodegradable drug-eluting implants that provide sustained release of metronidazole and doxycycline. The drug-eluting implants were prepared using the compression molding technique. To fabricate the implants, polylactide-polyglycolide copolymers were premixed with metronidazole or doxycycline. The mixture was then compression molded and sintered to form implants of various sizes and geometries. An elution method and an HPLC assay were used to characterize the in vitro release rates of the antibiotics over a 28-day period. A bacterial inhibition test was also carried out to determine the bioactivity of released antibiotics. The concentrations of both metronidazole and doxycycline were much greater than the minimum inhibitory concentration of Escherichia coli for up to 3 and 4 weeks, respectively, and the bioactivities of the antibiotics remained high after the fabrication process. Furthermore, the initial burst could be minimized and the release rate could be reduced by increasing the size of the implants and by adopting low drug to polymer ratios. By using this compression molding technique and appropriate processing parameters, we will be able to fabricate biodegradable implants of various types of antibacterial drugs for long-term local deliveries. Eventually, biodegradable drug-eluting implants may be used to treat various periodontal diseases.