VaIproic Acid Extended Release Formulation Development and In-Vitro In-Vivo Correlation (IVIVC) development

摘要

Several extended release-formulations of Valproic Acid were developed utilizing Banner Pharmacaps' Versatrol(TM) Technology. The Valproic Acid fill formulation is a homogeneous solid matrix consisting of Banner's Proprietary VersatrolTM Technology. Four formulations, selected in part based on in-vitro dissolution studies were evaluated in an in-vivo human clinical study together with the Reference Listed Drug (Depakote(R) ER). In vivo data indicated the utility of the VersatrolTM Technology for the sustained release of Valproic Acid from two of the four formulations; however the overall plasma levels were lower than from the Reference Listed Drug. It is noted that Pharmacokinetic parameters demonstrated a sustained release profile. Further to the in vivo study, a discriminating dissolution method was developed for use in generating the necessary TVTVC to support further formulation development.