title: In vitro-in vivo correlation for nevirapine extended release tablets.
abstract: An in vitro-in vivo correlation (IVIVC) for four nevirapine extended release tablets with varying polymer contents was developed. The pharmacokinetics of extended release formulations were assessed in a parallel group study with healthy volunteers and compared with corresponding in vitro dissolution data obtained using a USP apparatus type 1. In vitro samples were analysed using HPLC with UV detection and in vivo samples were analysed using a HPLC-MS/MS assay; the IVIVC analyses comparing the two results were performed using WinNonlin. A Double Weibull model optimally fits the in vitro data. A unit impulse response (UIR) was assessed using the fastest ER formulation as a reference. The deconvolution of the in vivo concentration time data was performed using the UIR to estimate an in vivo drug release profile. A linear model with a time-scaling factor clarified the relationship between in vitro and in vivo data. The predictability of the final model was consistent based on internal validation. Average percent prediction errors for pharmacokinetic parameters were <10% and individual values for all formulations were <15%. Therefore, a Level A IVIVC was developed and validated for nevirapine extended release formulations providing robust predictions of in vivo profiles based on in vitro dissolution profiles.
authors.affiliation: Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA. sreeraj.macha@boehringer-ingelheim.com
authors.forename: Sreeraj
authors.initials: S
authors.lastname: Macha
authors.forename: Chan-Loi
authors.initials: CL
authors.lastname: Yong
authors.forename: Todd
authors.initials: T
authors.lastname: Darrington
authors.forename: Mark S
authors.initials: MS
authors.lastname: Davis
authors.forename: Thomas R
authors.initials: TR
authors.lastname: MacGregor
authors.forename: Mark
authors.initials: M
authors.lastname: Castles
authors.forename: Steven L
authors.initials: SL
authors.lastname: Krill
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003692:Delayed-Action Preparations; D006801:Humans; D016014:Linear Models; D015233:Models, Statistical; D019829:Nevirapine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D011108:Polymers; D013607:Tablets; D019829:Nevirapine