Investigation of the in vitro release of gentamicin from a polyanhydride matrix

Septacin(TM) is a sustained release formulation consisting of gentamicin su lfate dispersed in a biodegradable polyanhydride matrix. The polyanhydride matrix is a copolymer of erucic acid dimer (EAD) and sebacic acid in a 1:1 weight ratio. In vitro drug release was performed in both water and pH 7.4 phosphate buffer. The drug release in water was faster than that in the buf fer, which was the opposite of what would be expected based upon a faster p olymer hydrolysis rate in the buffer, Theoretical treatment of the data usi ng the Peppas model revealed that release in water was anomalous, while the release in pH 7.4 phosphate buffer was diffusion-controlled. Profound bead morphology differences were observed between beads in these two in vitro r elease media. Cracking was observed in beads in water and swelling with no apparent cracking was seen in beads in buffer. Concurrent monitoring of dru g and sebacic acid release indicated that drug release is not via surface e rosion. Osmotic effects were found to play little role in the in vitro drug release. There was no spectroscopic evidence of amide formation between th e drug and copolymer. Sulfate release was monitored along with drug release and the results indicate that there is ion-exchange occurring during the p H 7.4 in vitro release. It was subsequently demonstrated that gentamicin ca n form an insoluble salt with EAD. This salt formation explains the slower drug release in pH 7.4 phosphate buffer. (C) 2000 Elsevier Science B.V. All rights reserved.