Investigation of the in vitro release of gentamicin from a polyanhydride matrix.
Septacin¿trade mark omitted¿ is a sustained release formulation consisting of gentamicin sulfate 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 buffer, which was the opposite of what would be expected based upon a faster polymer hydrolysis rate in the buffer. Theoretical treatment of the data using 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 release media. Cracking was observed in beads in water and swelling with no apparent cracking was seen in beads in buffer. Concurrent monitoring of drug and sebacic acid release indicated that drug release is not via surface erosion. Osmotic effects were found to play little role in the in vitro drug release. There was no spectroscopic evidence of amide formation between the drug and copolymer. Sulfate release was monitored along with drug release and the results indicate that there is ion-exchange occurring during the pH 7.4 in vitro release. It was subsequently demonstrated that gentamicin can form an insoluble salt with EAD. This salt formation explains the slower drug release in pH 7.4 phosphate buffer.
Stephens
D
D
Advanced Drug Delivery, Hospital Products Division, Abbott Laboratories, Department 97d, 100 Abbott Park Road, Abbott Park, IL, USA. stephend@hpd.abbott.com
Li
L
L
Robinson
D
D
Chen
S
S
Chang
H
H
Liu
R M
RM
Tian
Y
Y
Ginsburg
E J
EJ
Gao
X
X
Stultz
T
T
D003652:Decanoic Acids / Q000737:chemistry; D003692:Delayed-Action Preparations; D003998:Dicarboxylic Acids; D004883:Erucic Acids / Q000737:chemistry; D005839:Gentamicins / Q000008:administration & dosage* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D009994:Osmolar Concentration; D012995:Solubility; D013431:Sulfates / Q000737:chemistry
D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D003998:Dicarboxylic Acids; D004883:Erucic Acids; D005839:Gentamicins; D013431:Sulfates; C049811:erucic acid; C011107:sebacic acid