Mathematical prediction of pharmacokinetic parameters-an in-vitro approach for investigating pharmaceutical products for IVIVC

Abstract

A key approach in development of any pharmaceutical dosage form is to establish applicability and assuring the quality safety of its product. IVIVC establishes an important link between the in-vitro dissolution and the in-vivo release of the drug under study. Utilizing an IVIVC approach in advancement of new pharmaceutical reduces the figured human studies and pre-clinical studies, as it serves as surrogate for bioequivalency. It validates the drug dissolution studies, and thus assists in quality control for assertive scale up. The aim of this study is to compare and investigate the predicted plasma concentration-time profile of metronidazole (model drug) from in vitro dissolution results of formulated product with two reference marketed products, Brand A and Brand B using mathematical convolution approach for IVIVC. In-vitro drug dissolution tests were conducted using the USP type-II at 50 rpm with 900 mL of 0.1 M HCl as dissolution medium. Predicted blood levels along with the derived pharmacokinetic parameters (Tmax, Cmax, and AUC) were assessed, for all the three products with the comparable in-vivo data reported in the well authentic published literature. The predicted pharmacokinetic parameters obtained from F1, Brand A and Brand B were found to be similar to that of the values obtained from literature. The predicted Cmax and AUC were found to be 7.09 ± 0.18 μg mL−1 and 90.17 ± 11 μg mL-1 h for F1, 6.41 ± 0.17 μg mL−1 and 81.68 ± 09 μg mL-1 h for Brand A, 6.12 ± 0.11 μg mL−1 and 77.13 ± 14μgmL−1 h for Brand B. F1 imparts more predictability and validity of the approach in comparison to marketed formulations. Keywords: IVIVC, Metronidazole, Convolution, in vitro dissolution