In vitro–in vivo correlation (IVIVC) models for metformin after administration of modified‐release (MR) oral dosage forms to healthy human volunteers

The objective of the current study was to develop and evaluate the internal predictability for level C and A in vitro–in vivo correlation (IVIVC) models for prototype modified‐release (MR) dosage forms of metformin. In vitro dissolution data for metformin were collected for 22 h using a USP II (paddle) method. In vivo plasma concentration data were obtained from 8 healthy volunteers after administration of immediate‐release (IR) and MR dosage forms of metformin. Linear level C IVIVC models were developed using dissolution data at 2.0 and 4.0 h and in vitro mean dissolution time (MDT). A deconvolution‐based level A model was attempted through a correlation of percent in vivo input obtained through deconvolution and percent in vitro dissolution obtained experimentally. Further, basic and extended convolution level A IVIVC models were attempted for metformin. Internal predictability for the IVIVC models was assessed by comparing observed and predicted values for Cmax and AUC(INF). The results suggest that highly predictive level C models with prediction errors (%PE) of