Development and Evaluation of Internal and External Predictability of Metoclopramide Hydrochloride Modified Release Formulations: An Establishment of Level A In vitro and In vivo Correlation

Abstract: The objective of this study was to develop an in vitro–in vivo correlation (IVIVC) model for hydrophilic matrix sustained-release (SR) Metoclopramide formulations. The in vitro release characteristics of the drug were determined using USP apparatus II at 50 rpm, pH 6.8. In vivo plasma concentrations and pharmacokinetic parameters in healthy human subjects were obtained after administering oral dose, developed SR formulations and marketed immediate-release (IR) products. The similarity factor f2 was used to compare the dissolution data. The IVIVC model was developed using pooled fraction dissolved and fraction absorbed of developed SR formulations i.e. fast, medium and slow release and marketed immediate-release (IR) products. An in vitro-in vivo correlation (IVIVC) was established for sustained release tablet by deconvolution using data from an immediate-release treatment as the characteristic response. To assess the correlation between in vitro dissolution uniqueness and in vivo absorption performance of Metoclopramide sustained release (SR) and immediate release (IR) tablet in human subjects. The established IVIVC was evaluated internally by predicting data used to develop and externally by predicting data not originally included in developing the IVIVC model. The observed low prediction errors for Cmax and AUC demonstrated that the Metoclopramide IVIVC model was valid. Keywords: Metoclopramide Hydrochloride, Modified Release, Level A Correlation, Internal And External Prediction Errors.