A MECHANISTIC STUDY OF ANTIBIOTIC RELEASE FROM BIODEGRADABLE POLY(D,L-LACTIDE) CYLINDERS

Biodegradable poly(d,l-lactide) (PDLLA) coated gentamicin/PDLLA and cefazolin/PDLLA cylinders were made for the controlled release of antibiotics. The antibiotic release properties as well as release mechanisms (i.e., diffusion through channel, osmotic pressure, and polymer degradation) were investigated. Water soluble antibiotics could only be released through channels formed by connected drug particles and through polymer mass loss. Osmotic pressure played a key role by turning isolated drug clusters into connected channels through fracturing of the polymer matrix. The osmotic process of turning isolated clusters into connected clusters required time. This in turn gave a more gradual and sustained release than pure diffusion-through-channel release (i.e., without osmotic pressure effect involved). The effect of polymer biodegradation on release was significant when polymer mass loss started and at the same time there was a substantial amount of drug remaining in the device. In this case drug was released along with polymer mass loss. The cylinder core degraded faster than the cylinder shell when the longer gentamicin device was incubated in salt eluent. Gentamicin sulfate remained in the core and therefore catalysed the polymer degradation. For the release into water or low osmotic eluent, three critical factors affected the release properties, namely drug loading, drug particle size, and length of the coated cylinder. For antibiotic release from the coated cylinder with drug loading below the percolation threshold, as in the case of the 30 wt% loaded gentamicin cylinder, the mechanism was a combination of pure diffusion-through-channels and osmotic pressure-induced diffusion through-channels. Above the threshold (e.g., 40 wt%-50 wt% loaded gentamicin cylinders), the release was purely diffusion-through-channels and was very fast. A large drug particle size resulted in a large degree of pure diffusion-through-channel at the same drug loading. The longer the cylinder, the longer and the slower the release. This gave a convenient method of being able to adjust the release properties.