In vivo-in vitro study of biodegradable methadone delivery systems.
Three one-week controlled-release methadone formulations: polylactic acid microspheres (F-PLA) and poly(lactide-co-glycolide) microspheres (F-PLGA) with 24 and 30% methadone content, respectively, and an implant of 50:50 poly(lactide-co-glycolide): methadone, were evaluated in vitro and in vivo. The implant released the total amount of methadone in vitro while microsphere formulations released the methadone incompletely, 63% from F-PLA and 85% from F-PLGA in a week. Methadone release in vivo was estimated by deconvolution, F-PLGA giving a bioavailability >99% (methadone was totally released in 48h), while the estimated bioavailability of F-PLA was lower than expected. The bioavailability of the implant by deconvolution was around 60%, but absence of methadone in the implant indicated its complete release. These differences are due to an increase in methadone clearance after 72 h of the in vivo experimental period had passed, disturbing a good in vivo-in vitro correlation. A linear correlation between in vitro methadone release and in vivo release calculated from the amount of drug remaining within the implant, was found until the drug was completely released.
Negrin
C M
CM
Departamento de Ingeniería Química y Tecnología Farmaceutica, Facultad de Farmacia, Universidad de La Laguna, Tenerife, Spain.
Delgado
A
A
Llabrés
M
M
Evora
C
C
D000818:Animals; D001673:Biodegradation, Environmental; D001682:Biological Availability; D004337:Drug Carriers; D066298:In Vitro Techniques; D019344:Lactic Acid; D008297:Male; D008691:Methadone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011091:Polyesters; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers
D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D008691:Methadone