DEVELOPMENT OF AN INJECTABLE SUSTAINED-RELEASE FORMULATION OF MORPHINE - ANTINOCICEPTIVE PROPERTIES IN RATS

The antinociceptive actions of morphine incorporated into an injectabl e chitosan-based gel were investigated in rats. Subcutaneous administr ation of 4.8 mg/kg morphine sulphate in a gel composed of N,O-carboxym ethylchitosan (NOCC) and chitosan resulted in significant antinocicept ion within 10 min that was maximal at 60 min and persisted for 6 h. In contrast, the same dose of morphine sulphate injected in sterile sali ne produced maximal responses at 30 min but only persisted for 2 h. NO CC/chitosan gel was easily injectable using a 22 guage needle and appe ars stable in long-term storage. No local or systemic adverse effects other than morphine-induced sedation were observed either at the time of injection or during the subsequent 48 h. We conclude that gels comp osed of chitosan and chitosan derivatives are effective matrices for s ustained-release formulations of opioid analgesics capable of providin g long-lasting antinociception.