Preparation and characterization of biodegradable poly(l-lactic acid) gentamicin delivery systems

In the last two decades, localized antibiotic therapy has emerged as an important approach to treating orthopedic infections. This paper describes the preparation and in vitro evaluation of biodegradable, poly(l-lactic acid), implants for localized delivery of gentamicin sulfate for the treatment of osteomyelitis. Cylindrical, poly(l-lactic acid) implants containing gentamicin sulfate were obtained by compression of microcapsules prepared by a nonsolvent-induced, coacervation process. Mean particle size distributions of the microcapsules, based on volume, ranged from 278 to 444 μm. The gentamicin sulfate loading of the microcapsules, after a methylene chloride-water extraction procedure, exceeded 95% of the theoretical value. In vitro dissolution studies on microcapsules and implants with drug loading varying from 5 to 67% w/w indicated that the rate of gentamicin sulfate released from both microcapsules and implants increased, while the dissolution half-life (T₅₀) decreased, exponentially, with an increase in drug loading. Profiles of amount of drug dissolved at different times followed a square-root-time relationship. All batches of microcapsules and implants released greater than 80% gentamicin sulfate within 3 weeks. In comparison, previous studies in this laboratory have indicated that conventional, nonbiodegradable polymethylmethacrylate implants, containing gentamicin or tobramycin, show incomplete and poorly controlled drug release during the same time period.