A computer-aided simulation approach in the development of a prolonged release formulation

Prolonged medication with diltiazem has proved advantageous in the treatment of coronary insufficiency and arterial hypertension. Consistently, a number of extended release formulations, based on different retardation mechanisms, have been proposed. In the present work two prolonged release oral formulations containing diltiazem, one intended for twice-a-day and one for once-a-day administration, were tested for in vitro behaviour; the in vitro release test had been opportunely validated using an in vitro-in vivo correlation approach. On the basis of in vitro release profiles, simulations were effected, using a computer program previously developed, in order to generate the plasma levels that could be expected on single dosing of the two formulations. The two formulations were then tested in vivo and the measured plasma profiles were compared with those predicted from in vitro data. For both formulations, a good agreement was found between the measured and the simulated plasma levels, thus demonstrating the usefulness of the simulation approach in the formulative development.