title: Predicting the in vivo release from a liposomal formulation by IVIVC and non-invasive positron emission tomography imaging.
abstract: This study aimed to predict the in vivo performance from the in vitro release of a low-molecular weight model compound, [(18)F]-2-fluoro-2-deoxy-d-glucose ([(18)F]FDG), from liposomes and by means of positron emission tomography (PET). Liposomes composed of hydrogenated phosphatidylcholine (HPC) were prepared by a freeze-thaw method. Particle size distribution was measured by dynamic light scattering (DLS). In vitro release was examined with a dispersion method detecting the radioactivity of [(18)F]FDG. In vivo release of [(18)F]FDG, following i.p. injection of the liposomes in rats, was determined by using a Micro-PET scanner. Convolution was performed to predict the in vivo profiles from the in vitro data and to establish an in vitro-in vivo correlation (IVIVC). The in vivo predictions slightly underestimated the experimentally determined values. The magnitude of the prediction errors (13% and 19%) displayed a satisfactory IVIV relationship leaving yet room for further improvement. This study demonstrated for the first time the use of PET in attaining an IVIVC for a parenterally administered modified release dosage form. It is therefore possible to predict target tissue concentrations, e.g., in the brain, from in vitro release experiments. IVIVC using non-invasive PET imaging could thus be a valuable tool in drug formulation development, resulting in reduced animal testing.
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55099 Mainz, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Hühn
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Buchholz
authors.forename: Gamal
authors.initials: G
authors.lastname: Shazly
authors.forename: Stephan
authors.initials: S
authors.lastname: Maus
authors.forename: Oliver
authors.initials: O
authors.lastname: Thews
authors.forename: Nicole
authors.initials: N
authors.lastname: Bausbacher
authors.forename: Frank
authors.initials: F
authors.lastname: Rösch
authors.forename: Mathias
authors.initials: M
authors.lastname: Schreckenberger
authors.forename: Peter
authors.initials: P
authors.lastname: Langguth
mesh_terms: D000818:Animals; D019788:Fluorodeoxyglucose F18; D008081:Liposomes; D010316:Particle Size; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats
chemical_list: D008081:Liposomes; D019788:Fluorodeoxyglucose F18