BIOERODIBLE NARCOTIC ANTAGONIST DELIVERY DEVICE

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The principal objective of this research is to develop an implantable, bioerod drug delivery device that releases naltrexone by an erosion-controlled process by kinetics approaching zero order. The naltrexone is dispersed in a crosslinked poly(ortho ester) that contains hydrolytically labile linkages in the matrix. Release of naltrexone is controlled by a combination of diffusion and rate at which these linkages cleave. Because poly(ortho esters) are acid sensitive rate of hydrolysis can be controlled by means of incorporated acidic excipients or by copolymerized monomers that contain pendant carboxylic acid groups. Rate of polymer hydrolysis increases with increasing concentration of these excipients or acidic monomers. In addition, rate of hydrolysis increases as the hydrophilicity of the polymer increase. Thus, fairly precise control over rate of polymer hydrolysis and consequent drug release can be established. Cylindrical devices can be readily produced by simple extrusion of a viscous liquid prepolymer and then cured at moderate temperatures, or microspheres can be produced by dispersing the viscous liquid prepolymer in an inert medium, followed by curing. Poly(ortho esters) have been extensively investigated by the principal Investigator for the release of levonorgestrel, and toxicological studies for an IND filing are about to be initiated. We propose to develop delivery system useful for the treatment of narcotic addiction and to gain a better understanding of the release of therapeutic agents having water solubilities considerably higher than the very water- insoluble levonorgestrel.