Development and validation of an in vitro–in vivo correlation (IVIVC) model for propranolol hydrochloride extended-release matrix formulations

Abstract

The objective of this study was to develop an in vitro – in vivo correlation (IVIVC) model for hydrophilic matrix extended-release (ER) propranolol dosage formulations. The in vitro release characteristics of the drug were determined using USP apparatus I at 100 rpm, in a medium of varying pH (from pH 1.2 to pH 6.8). In vivo plasma concentrations and pharmacokinetic parameters in male beagle dogs were obtained after administering oral, ER formulations and immediate-release (IR) commercial products. The similarity factor f 2 was used to compare the dissolution data. The IVIVC model was developed using pooled fraction dissolved and fraction absorbed of propranolol ER formulations, ER-F and ER-S, with different release rates. An additional formulation ER-V, with a different release rate of propranolol, was prepared for evaluating the external predictability. The results showed that the percentage prediction error (%PE) values of C max and AUC 0–∞ were 0.86% and 5.95%, respectively, for the external validation study. The observed low prediction errors for C max and AUC 0–∞ demonstrated that the propranolol IVIVC model was valid.

Synergistic Modeling of in-vitro and in-vivo data via Stochastic Kriging with Qualitative Factors (SKQ)

“…Since a bioequivalence study is needed to validate a new formulation, which takes a lot of time and money, and as asserted before, time and money are always significant issues. Therefore, in pharmaceutical studies, the application of IVIVC is very important [3].…”

“…Performing the deconvolution needs a reference product. The reference product can be an immediate release product or an intravenous solution [1], which in Cheng's et al [3] [1], like the in-vivo absorption studies performed in the study by Cheng et al [3] study. In that study, all of the six male Beagle dogs were fasted for twelve hours before the experiment, and they just had access to unlimited water.…”

“…Another issue is that in order to obtain the dissolution characteristics of the ER dosage form, the same method should be used for all formulations. In Cheng et al [3] study, the release characteristic of all the propranolol extended-release tablets were determined using USP apparatus I (basket) with a rotation speed of rpm and maintained at 37°C [3].…”

“…To treat high blood pressure, the usual dose of propranolol is 120-240 mg divided in 2-3 doses per day; hence, there is a need to study the once-daily extended-release dosage formulation. Many studies had been reported with respect to controlled-release formulations, while none of them had focused on propranolol matrix ER formulations until Cheng et al [3] developed an IVIVC model for propranolol matrix ER dosage formulations.…”

“…proposed by Wang et al [36] to model in-vivo and in-vitro data together for improved fitting of in-vivo behavior. The data used in this work are taken from Cheng et al [3].…”