Modeling the pharmacokinetics of Extended Release pharmaceutical systems
Multi-scale and/or multi-disciplinary approach to process-product innovation
Controlled Release of the Active Ingredient: Mechanisms, Devices & Analysis (T3-2P)
Keywords: extended release pharmaceutical systems, pharmacokinetics, compartmental modeling
Gaetano Lamberti*, Michela Di Muria, Giuseppe Titomanlio
Department of Chemical and Food Engineering - University of Salerno
Via Ponte Don Melillo - 84084 Fisciano - www.dica.unisa.it
*glamberti@unisa.it Tel. +39089964077
In this work a conventional method to model the drug hematic concentration after a pharmaceutical system oral administration was improved by adding the ability of modeling the lag time typical of the extended release formulations.
Usually, the body was modeled as a single or as a couple of compartments, i.e. one or two ensembles of blood and tissue more or less perfused (rich in blood). The transient mass balances within these compartments (which from a chemical engineers’ point of view could be taken as reactors) constitute the model equations whose solution is the desired drug concentration profile in blood. However, the traditional approach is based on the full availability of the drug at the site of absorption at the same instant of the administration. For a number of systems this is a good approximation (fast release tablet, highly soluble drugs), but this is incorrect for several systems (extended release tablet, scarcely soluble drugs). Usually, the prediction of the drug concentration profile in blood, starting from the release kinetic data measured In Vitro, i.e. in laboratory, for system which exhibit a lag time, was performed by means of purely statistic tools (various level of IVIVC, In Vitro-In Vivo Correlations, ranging from the worst, level C, to the best, level A), or on the basis of non-compartmental models which require cumbersome calculations.
Here we propose a very simple model which relates the availability of the drug in the blood to the release kinetics as measured by In Vitro tests. The improved model was applied to describe cases, taken from literature, for which both the In Vitro (% of drug release versus time, in a vessel) and the In Vivo (concentration of drug in blood versus time, in humans) data are available.
Studying the case of divalproex sodium release from three different formulations (fast, medium and slow release), the model was tuned on the basis of the data for one formulation (medium release), and then it was proved to be predictive (the same of a Level A IVIVC) for the fast and the slow release formulations.
Proposed approach, which was proven able to satisfactorily play the role of a Level A IVIVC, is really simple and requires the availability of a limited set of data (at least one couple of In Vitro and In Vivo data). Therefore, it can be of aid for rational development, optimization, and evaluation of controlled-release dosage forms and manufacturing process.
Presented Tuesday 18, 13:30 to 15:00, in session Controlled Release of the Active Ingredient: Mechanisms, Devices & Analysis (T3-2P).
