Extended-release formulation of morphine for subcutaneous administration.

Pain arising from cancer tends to be chronic and chemotherapy of cancer pain usually requires narcotics. Most injectable narcotics, however, have short half-lives (T1/2) and require either continuous infusion or repeated frequent injections which are both inconvenient and uncomfortable. An extended-release formulation of morphine sulfate (Depo/Morphine) in a lipid-based drug-delivery system was characterized and tested in an animal model. The encapsulation efficiency was 53% +/- 4%, and the in vitro release T1/2 in human plasma at 37 degrees C was 12.1 +/- 1.1 days. Following s.c. administration of Depo/Morphine, the total amount of morphine remaining at the s.c. injection site decreased monoexponentially with a T1/2 value of 2.59 +/- 0.16 days as compared with 0.46 +/- 0.04 h following the injection of unencapsulated morphine. The morphine concentration in plasma also decreased monoexponentially with a T1/2 value of 8.33 +/- 2.13 days as compared with 0.45 +/- 0.21 h for unencapsulated morphine. Cataleptic behavior was observed in mice injected with unencapsulated morphine but not in those given an identical dose of morphine in the form of Depo/Morphine. In conclusion, Depo/Morphine has potential as an extended-release formulation of morphine and may be useful in chemotherapy of cancer pain as well as in maintenance therapy of narcotic addicts.