In vivo evaluation of a new sustained-release formulation of morphine.
The pharmacokinetics of a novel sustained-release oral formulation of morphine have been evaluated. The formulation consisted of tablets containing a morphine-EudragitL complex (MEC) which had shown good sustained-release properties in previous in vitro dissolution studies. MEC tablets were administered orally to beagle dogs and the morphine plasma levels and pharmacokinetic parameters obtained were compared with those obtained with MST Continus, a commercially available sustained release form of morphine. Blood samples were withdrawn up to 12 h after dosing and plasma morphine concentrations were determined by HPLC with electrochemical detection. Both formulations presented a relatively rapid absorption of morphine with similar values of Cmax (MST: 53 ng/ml; MEC: 50 ng/ml) and Tmax (MST: 86 min; MEC: 88 min), and prolonged morphine plasma levels. Mean plasma morphine concentrations were higher for the MEC tablets than for MST tablets during the terminal phase of the corresponding curves and the mean AUC(0-12h) for MEC tablets was 138% of that obtained with MST tablets. Our findings indicate that MEC tablets can produce prolonged plasma levels of morphine and could be an alternative to commercially available morphine sustained-release forms.
Araico
A
A
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Spain.
Saadeddin
A
A
Torres-Molina
F
F
Peris
J E
JE
D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004285:Dogs; D005079:Excipients; D005260:Female; D006207:Half-Life; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D011109:Polymethacrylic Acids; D013056:Spectrophotometry, Ultraviolet
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D005079:Excipients; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D009020:Morphine