Prolonged release of morphine alkaloid from a lipophilic suppository base in vitro and in vivo.
The in vitro release characteristics of four suppository formulations of morphine (15 mg) were investigated using the USP rotating basket dissolution apparatus. Morphine hydrochloride in polyethylene glycol (PEG), a hydrophilic suppository base, morphine alkaloid in PEG and morphine hydrochloride in Novata BBC (a lipophilic suppository base) completely released the drug within 25 min whereas, morphine alkaloid in Novata BBC (MAN) released the drug over 10 h. The absorption of the morphine hydrochloride/PEG (MHP) suppository was compared with that of a 15 mg oral solution in eight patients with malignant disease in a crossover design. Time of peak plasma morphine concentration (tmax) was similar for both preparations (1.8 +/- 1.6 h and 1.2 +/- 0.5 h, respectively; p > 0.05), showing that the MHP suppository was rapidly absorbed. The MAN and MHP suppositories were then compared in a further nine patients in a crossover design. Prolonged release of morphine from the MAN suppository was also evident in vivo as tmax (2.5 +/- 1.4 h) was significantly greater than that for the morphine hydrochloride/PEG suppository (0.7 +/- 0.3 h; p < 0.002). There was no significant difference in AUC (0-7 h) (34.5 +/- 19.2 versus 38.9 +/- 16.1 ng.h/ml, respectively; p > 0.05) indicating a similar amount of morphine absorbed. Plasma morphine concentrations were more sustained for 7 h after dosage with the MAN suppository, with lower peak (8.3 +/- 4.9 and 12.3 +/- 6.6 ng/ml, respectively) and higher 6 h plasma morphine concentrations (5.81 +/- 4.85 and 3.30 +/- 1.0 ng/ml, respectively; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Morgan
D J
DJ
Victorian College of Pharmacy, Parkville, Melbourne, Australia.
McCormick
Y
Y
Cosolo
W
W
Roller
L
L
Zalcberg
J
J
D000285:Administration, Rectal; D000368:Aged; D001682:Biological Availability; D003692:Delayed-Action Preparations; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010146:Pain / Q000188:drug therapy; D011092:Polyethylene Glycols; D012995:Solubility; D013488:Suppositories
D003692:Delayed-Action Preparations; D013488:Suppositories; D011092:Polyethylene Glycols; D009020:Morphine