Development and Validation of an In Vitro and In Vivo Correlation Model in NZ Rabbit for Topiramate Extended Release Capsules

Abstract

The purpose of this study was to build an in vitro-in vivo correlation model for topiramate extended release capsules. Three formulations with different release rate were developed by varying the percentage of the rate controlling polymer ethylcellulose and pore former hypromellose. In vitro dissolution of all formulations was performed by united states of phaemacopiea type I apparatus using multimedia dissolution conditions such as 0.1 N hydrochloric acid pH 1.2 for initial 2 h followed by phosphate buffer pH 6.8 for the rest of 22 h. Total dissolution time was up to 24 h. In vivo pharmacokinetic profile of the immediate release suspension and different extended release formulations were investigated in rabbit model after single oral administration of topiramate at a dose of 10.33 mg/kg in vitro-in vivo correlation model was established by using two stage numerical deconvolution approaches. Unit impulse response was obtained from pharmacokinetic profile of immediate release suspension which was used as a reference formulation. A linear correlation model with a time scaling factor was found to be useful to build level A correlation. The developed in vitro-in vivo correlation model was validated as per food drug administration guideline, and the % prediction error for maximum concentration observed (Cmax) and area under the concentration time curve was within acceptable limits of below 15%. The utility of the developed model was evaluated by testing the targeted formulations. The observed % prediction error was 2.61 and -0.43 for Cmax and area under the concentration time curve, respectively suggesting the usefulness of the present in vitro-in vivo correlation model.