Development of polylactic/glycolic acid delivery systems for use in treatment of narcotic addiction

Abstract

Implantable polylactic/glycolic acid matrix systems have successfully provided the sustained release of naltrexone to mice for periods of up to 200 days. In vitro and in vivo release rates have been determined by measuring chemical concentrations in pH 7 buffer solution and urine, respectively, and in vivo efficacy has been measured by direct challenge with morphine (Dewey-Harris mouse tail-flick test). Dosage forms of small implantable cylinders, 1/16'' diameter, (25 mg/rod, one rod/mouse) containing 33% by weight naltrexone pamoate in 90 L(+)/10 polylactic/glycolic acid have sustained the delivery of chemical for 20 days. Delivery of chemical from dosage forms of 1/16'' diameter spherical beads (3 mg/bead, 3 beads/mouse) containing 33% by weight naltrexone base in 90 L(+)/10 polylactic/glycolic acid was sustained for 60 days. Earlier a similar bead type dosage form of 75 L(+)/25 polylactic/glycolic acid containing 50% by weight naltrexone base and coated with the pure polymer provided controlled release for 25 days. Polymerization conditions which incorporate the use of pharmacologically suitable catalysts and yield products reproducibly have have been delineated. Techniques for sterilization of the final implant have been screened.