Biodegradable Controlled Antibiotic Release Devices for Osteomyelitis: Optimization of Release Properties

Abstract— Controlled antibiotic release films, melt‐extruded cylinders, and suspension‐extruded/coated cylinders were manufactured from biodegradable poly(d, l‐lactide) (PDLLA) and poly(d, l‐lactide‐co‐∈‐caprolactone). These devices have potential application in the treatment of osteomyelitis. The in‐vitro release properties of the devices were examined with drug loadings varying from 16 to 50%. Gentamicin sulphate films and melt‐extruded gentamicin/PDLLA cylinders demonstrated a large initial burst and incomplete release. The films and melt‐extruded cylinders made from poly(d, l‐lactide‐co‐∈‐caprolactone), low mol. wt poly(d, l‐lactide), and a mixture of d, l‐lactic acid oligomer and high mol. wt poly(d, l‐lactide), did not remain intact during the entire release period. While this is undesirable, these materials do have the advantage of not requiring a processing temperature of greater than 110°C. Antibiotic release from high mol. wt PDLLA‐coated gentamicin/PDLLA cylinders, with 40 and 50% loading, was very rapid. The antibiotic could only diffuse out through the open ends of the cylinder. Coated gentamicin sulphate cylinders with 20 and 30% drug loading gave the most promising properties in terms of a small initial burst, and a gradual and sustained release. The release rate and duration from the coated cylinders could be adjusted by cutting the cylinder into different lengths; the time required for 90% of the entrapped gentamicin to be released into water from 30% loaded PDLLA‐coated cylinders 0·2, 0·4, 0·7 and 1 cm in length was 1000, 1700, 2300, and 2800 h, respectively. This offers a convenient method to adjust the release to meet the specific antibiotic requirement of different patients. Cephazolin and benzylpenicillin were found to be unsuitable for sustained release longer than 300 h due to the hydrolytic instability of the drugs in water.