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

Biodegradable poly(d,l-lactide) (PDLLA) coated gentamicin/PDLLA and ce fazolin/PDLLA cylinders were made for the controlled release of antibi otics. The antibiotic release properties as well as release mechanisms (i.e., diffusion through channel, osmotic pressure, and polymer degra dation) were investigated. Water soluble antibiotics could only be rel eased through channels formed by connected drug particles and through polymer mass loss. Osmotic pressure played a key role by turning isola ted drug clusters into connected channels through fracturing of the po lymer matrix. The osmotic process of turning isolated clusters into co nnected clusters required time. This in turn gave a more gradual and s ustained release than pure diffusion-through-channel release (i.e., wi thout osmotic pressure effect involved). The effect of polymer biodegr adation on release was significant when polymer mass loss started and at the same time there was a substantial amount of drug remaining in t he device. In this case drug was released along with polymer mass loss . The cylinder core degraded faster than the cylinder shell when the l onger gentamicin device was incubated in salt eluent. Gentamicin sulfa te remained in the core and therefore catalysed the polymer degradatio n. For the release into water or low osmotic eluent, three critical fa ctors affected the release properties, namely drug loading, drug parti cle size, and length of the coated cylinder. For antibiotic release fr om the coated cylinder with drug loading below the percolation thresho ld, as in the case of the 30 wt% loaded gentamicin cylinder, the mecha nism 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 d iffusion-through-channels and was very fast. A large drug particle siz e 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.