%0 Journal Article
%T IVIVC from Long Acting Olanzapine Microspheres
%A Susan D'Souza
%A Jabar A. Faraj
%A Stefano Giovagnoli
%A Patrick P. DeLuca
%J International Journal of Biomaterials
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/407065
%X In this study, four PLGA microsphere formulations of Olanzapine were characterized on the basis of their in vitro behavior at 37¡ãC, using a dialysis based method, with the goal of obtaining an IVIVC. In vivo profiles were determined by deconvolution (Nelson-Wagner method) and using fractional AUC. The in vitro and in vivo release profiles exhibited the same rank order of drug release. Further, in vivo profiles obtained with both approaches were nearly superimposable, suggesting that fractional AUC could be used as an alternative to the Nelson-Wagner method. A comparison of drug release profiles for the four formulations revealed that the in vitro profile lagged slightly behind in vivo release, but the results were not statistically significant ( ). Using the four formulations that exhibited different release rates, a Level A IVIVC was established using the deconvolution and fractional AUC approaches. A nearly 1£¿:£¿1 correlation ( ) between in vitro release and in vivo measurements confirmed the excellent relationship between in vitro drug release and the amount of drug absorbed in vivo. The results of this study suggest that proper selection of an in vitro method will greatly aid in establishing a Level A IVIVC for long acting injectables. 1. Introduction Establishing an IVIVC (in vitro in vivo correlation) remains a challenge for non-oral dosage forms like long acting injectables. One reason for the lack of IVIVC is the dearth of in vitro methods that are simple to set up and use, while suitably mimicking in vivo conditions. The benefits of establishing an in vitro in vivo correlation (IVIVC) have been enumerated in numerous pharmaceutical publications spanning the last three decades. Indeed, IVIVC has remained a topic of constant discussion with several dosage forms, especially solid orals, since the publication of an IVIVC guidance by the FDA in 1997 [1]. The goal of an IVIVC is to establish a relationship between the in vitro dissolution behavior and in vivo performance of a drug product. An IVIVC is generally described by a linear relationship between parameters derived from the in vitro and in vivo experiments as quantified by the Pearson correlation. As defined by the FDA guidance, these correlations have been classified under four categories.(i)Level A, the highest correlation, is a point to point correlation between in vitro dissolution and in vivo absorption over time. With a Level A correlation, the in vitro dissolution profiles are generally superimposable with in vivo absorption curves or may be made superimposable by use of an appropriate
%U http://www.hindawi.com/journals/ijbm/2014/407065/