The pharmacokinetic profiles of two variations of a sustained release morphine sulfate formulation intended for once-daily administration

The pharmacokinetic profiles of 2 once-daily microgranulated sustained release (SR) morphine sulfate 60mg capsule formulations, differing only in coating excipients (A and B; Ethypharm QD((R))), were compared with the pharmacokinetic profile of a 60mg capsule containing SR morphine sulfate microgranules (C; M-Eslon((R))) intended for twice-daily administration. A single dose was given to 12 healthy male volunteers after overnight fasting. Blood samples were drawn over the 48 hours following administration, and a validated high performance liquid chromatography method was used to analyse plasma morphine and morphine-6-glucuronide (M6G) concentrations. Area under the plasma concentration-time curve values for A, B and C were 132, 137 and 145 mu g.h/L for morphine, and 1322, 1434 and 1324 mu g.h/L for M6G, showing bioequivalence for the extent of absorption. However, the respective peak plasma concentrations were 5.3, 4.9 and 11.7 mu g/L for morphine and 36.9, 38.3 and 97.2 mu g/L for M6G, showing a higher plasma concentration (because of a higher rate of release) for capsule C and providing evidence for the more extended release of morphine from capsules A and B. On the basis of these results, it can be concluded that these once-daily microgranulated SR morphine 60mg capsules are a promising alternative to twice-daily treatment.