An Implantable Dosage Form for the Treatment of Bone Infections

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Abstract
The object of this investigation was the development of an implantable sustained-release dosage form, for the treatment of bone infections. Cross-linked polydimethylsiloxane (PDMS) was used as the matrix material. The drug delivery system was prepared by incorporating tobramycin, as a free base (C18H37N5O9 · H2O) or as a sulfate salt [(C18H37N5O9)2 · 5H2SO4], into the matrix and molding into spherical beads. Following in vitro studies, the cumulative amount of drug released when plotted as a function of the square root of time was linear for both the base and the salt. The addition of glycerol to the matrix substantially accelerated the rate of drug release and the plots of cumulative amount of drug released continued to be linear as a function of the square root of time. The glycerol-incorporated beads swelled in contact with the aqueous medium but a negligible amount of glycerol was released even after exposure to the medium for 20 days. 13C solid-state and high-resolution NMR studies indicated that a fraction of the added glycerol participated in the cross-linking reaction of the polymer. The effect of the initial molecular weight of PDMS and the effect of the concentration of the cross-linker on the kinetics of drug release were investigated.