Physicochemical, pharmacokinetic and pharmacodynamic characterization of isradipine tablets for controlled release

Abstract

Isradipine is a dihydropyridine calcium channel blocker (CCB) commonly used as vasodilator with antihypertensive properties. A remote-controlled release formulation for isradipine would substantially improve the clinical outcomes of the patients requiring chronic long-term treatment. In this work, sustained release tablets of isradipine, composed of hydroxypropylmethyl cellulose (HPMC), have been produced by wet granulation and their in vitro and in vivo characterization was compared to a conventional tablet dosage form of immediate release as preliminary assessment. Tablets composed of 15.0% (wt/wt) HPMC exhibited a sustained release profile over a period of 24 hours. The release of isradipine followed a Fickian diffusion pattern obeying to the first order kinetics and the extent of absorption was even higher in comparison to the developed conventional tablets, which showed immediate drug release. In vivo studies were carried out in rabbits, showing that the extent of isradipine absorption from the developed tablets was higher in comparison to immediate release tablets due to the modified release profile obtained for the former (p < 0.05). Our results suggest that sustained release tablets of isradipine are an efficient solid dosage form to overcome the limitations encountered in conventional immediate release tablets.