PHARMACOKINETICS OF AN INJECTABLE SUSTAINED-RELEASE FORMULATION OF MORPHINE FOR USE IN DOGS

This study investigated the pharmacokinetics of morphine sulphate in a n injectable chitosan-based gel, Gels were made from a combination of N-O-carboxymethylchitosan (NOCC) and chitosan and were easily injectab le via a 22 gauge needle and appeared stable during long-term storage. Groups of six beagles were injected subcutaneously (s.c.) with 1.2 mg /kg morphine sulphate, either in sterile saline or in sterilized gels, and serial blood samples were withdrawn via a jugular catheter and la ter analysed for morphine concentrations using radioimmunoassay, Data were analysed according to noncompartmental pharmacokinetics, NOCC-bas ed gels resulted in significantly lower serum morphine concentrations at 10 and 30 min following injection but significantly higher concentr ations at all points from 120 to 480 min post; injection, Dogs receivi ng morphine gel exhibited equivalent or lesser variability in serum mo rphine concentrations than dogs receiving conventional morphine sulpha te, Pharmacokinetic analysis revealed that morphine release from the g el matrix was significantly prolonged but fully bioavailable, There we re no significant differences in either distribution (V-d) Or terminal elimination (t(1/2)) Dogs experienced no adverse effects other than t hose normally associated with morphine administration at the time of i njection but all dogs receiving the gel presented with an undefined st iffness the next day that resolved spontaneously within 48 h. We concl ude that carboxymethylchitosan-based gels hold considerable promise fo r the development of injectable sustained-release formulations of opio id analgesics.