GENTAMICIN POLY(LACTIC ACID) BLENDS AIMED AT SUSTAINED-RELEASE LOCAL ANTIBIOTIC-THERAPY ADMINISTERED PER-OPERATIVELY .2. THE CASE OF GENTAMICIN SULFATE IN HIGH-MOLECULAR-WEIGHT POLY(DL-LACTIC ACID) AND POLY(L-LACTIC ACID)

In a second attempt to design a simple gentamycin delivery system usable for local antibiotic therapy administered per-operatively, bioresorbable particles were made by grinding and sieving the solid masses resulting from the mixing of various amounts of gentamycin sulfate (GS) with two high molecular weight poly (lactic acids), namely amorphous poly (DL-lactic acid), PLA50P, and semicrystalline poly (L-lactic acid), PLA100P. Under these conditions, GS crystals for-med a solid dispersion within the polymer mass as deduced from SEM and X-ray diffraction. The polymer/drug particles were allowed to age in pH = 7.4, 0.13 M sodium phosphate buffer at 37-degrees-C. For PLA50P systems, the release profiles of gentamycin were biphasic with a burst effect followed by a phase of sustained release which lasted for more than two months. In contrast, the total loads were released within less than 6 h, in the case of PLA100P systems. The difference between release characteristics observed for the amorphous and the semicrystalline PLA/GS systems was due to differences of morphologies and not to differences of degradation rates. The dependence of release profiles on particle size and on drug load was also investigated. Only 0.5-1 mm, 10% w/w GS-loaded PLA50P particles gave release rates compatible with the requirements for local antibiotic therapy.