Norbert Mason ¹, Curt Thies ^{1 *}, Theodore J. Cicero ²

¹Department of Chemical Engineering, Washington University, St. Louis, MO 63130
²Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110

Keywords

Cyclazocine - injectable microcapsules, in vivo and in vitro release evaluated • Microcapsules, injectable - in vivo and in vitro release of cyclazocine evaluated • Dosage forms - injectable microcapsules, in vivo and in vitro release of cyclazocine evaluated • Narcotic antagonists - cyclazocine, in vivo and in vitro release from injectable microcapsules evaluated

Abstract

Injectable microcapsules containing 75% (w/w) cyclazocine, a narcotic antagonist, were prepared with dl-poly (lactic acid) as the coating material. Capsule fractions falling between 105 and 295 m released about 90% of their cyclazocine in 8 days of rotating-bottle extraction at 37° in pH 7.4 phosphate buffer. Although larger capsules released the drug somewhat more slowly, all capsules released cyclazocine far more rapidly than an ideal capsule should. This rapid release is attributed to macroscopic defects located in the capsule walls. The ability of the capsules to block the action of morphine in vivo was assessed by injection of a sesame seed oil suspension into Holtzman rats. A hot-plate test procedure was used to evaluate animal behavior. Capsule doses of 100-250 mg/kg to rats caused significant antagonism of morphine's analgesic effect for 14 days after injection. By Day 17, no antagonism occurred, indicating that the capsules completely released the drug in vivo between 14 and 17 days after injection.