title: A miniaturized in vitro release method for investigating drug-release mechanisms.
abstract: We have evaluated a miniaturized in vitro method, based on the μDISS Profiler™ technique that enables on-line monitoring of drug release from a 21 μl sample with 10 ml of release medium. Four model drugs in eight clinically used formulations, including both solid and non-solid drug delivery systems, were investigated. The acquired data were compared with historical in vitro release data from the same formulations. Use of the Weibull function to describe the in vitro drug-release profiles allowed discrimination between the selected formulations with respect to the drug-release mechanisms. Comparison of the release data from the same formulation in different in vitro set-ups showed that the methodology used can affect the mechanism of in vitro release. We also evaluated the ability of the in vitro methods to predict in vivo activity by comparing simulated plasma concentration-time profiles acquired from the application of the biopharmaceutical software GI-Sim to the in vitro observations. In summary, the simulations based on the miniaturized-method release data predicted the plasma profiles as well as or more accurately than simulations based on the historical release data in 71% of the cases and this miniaturized in vitro method appears to be applicable for both solid and non-solid formulations.
authors.affiliation: Department of Pharmacy, Uppsala University, Box 580, 751 23 Uppsala, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Ahnfelt
authors.affiliation: Department of Pharmacy, Uppsala University, Box 580, 751 23 Uppsala, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Sjögren
authors.affiliation: Department of Pharmacy, Uppsala University, Box 580, 751 23 Uppsala, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Axén
authors.affiliation: Department of Pharmacy, Uppsala University, Box 580, 751 23 Uppsala, Sweden. Electronic address: hans.lennernas@farmaci.uu.se.
authors.forename: H
authors.initials: H
authors.lastname: Lennernäs
mesh_terms: D002220:Carbamazepine / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D003198:Computer Simulation; D004008:Diclofenac / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D007408:Intestinal Absorption; D008790:Metoprolol / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D008904:Miniaturization; D008962:Models, Theoretical; D009288:Naproxen / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004008:Diclofenac; D002220:Carbamazepine; D009288:Naproxen; D008790:Metoprolol
keywords: GI-Sim; In vitro release methods; In vivo prediction; Release mechanisms; Weibull function