Prediction of in vivo plasma concentration–time profile from in vitro release data of designed formulations of milnacipran using numerical convolution method

Abstract

The aim of this study was to predict the in vivo plasma drug level of milnacipran (MIL) from in vitro dissolution data of immediate release (IR 50 mg and IR 100 mg) and matrix based controlled release (CR 100 mg) formulations. Plasma drug concentrations of these formulations were predicted by numerical convolution method. The convolution method uses in vitro dissolution data to derive plasma drug levels using reported pharmacokinetic (PK) parameters of a test product. The bioavailability parameters (Cmax and AUC) predicted from convolution method were found to be 106.90 ng/mL, 1138.96 ng/mL h for IR 50 mg and 209.80 ng/mL, 2280.61 ng/mL h for IR 100 mg which are similar to those reported in the literature. The calculated PK parameters were validated with percentage predication error (% PE). The % PE values for Cmax and AUC were found to be 7.04 and −7.35 for IR 50 mg and 11.10 and −8.21 for IR 100 mg formulations. The Cmax, Tmax, and AUC for CR 100 mg were found to be 120 ng/mL, 10 h and 2112.60 ng/mL h, respectively. Predicted plasma profile of designed CR formulation compared with IR formulations which indicated that CR formulation can prolong the plasma concentration of MIL for 24 h. Thus, this convolution method is very useful for designing and selection of formulation before animal and human studies.