Effect of casein incorporation on the release of Diltiazem HCl from Hypromellose-Based Matrix Tablets

Abstract

This study aimed to investigate the modifying effect of casein (CAS) on the release of a model basic drug, diltiazem HCl (DTZ), from hydroxypropyl methylcellulose (HPMC) matrices. The interaction of DTZ and CAS in solutions was investigated in terms of its stability and capacity. Granules of DTZ and CAS were prepared using a wet granulation. Granules were then mixed with HPMC and lactose and compressed into matrix tablets. The interaction of DTZ and CAS in the granules was characterized by DSC. The dependence of drug release from tablets on the pH and ionic strength of dissolution media was evaluated. The interaction was found to have an association constant of 21.09 mM and a binding capacity of 0.4358 mg DTZ / mg CAS. The release of DTZ was observed to become less sensitive to the pH of the dissolution medium with increasing the content of CAS. The DSC study showed an interaction between DTZ and CAS manifested by the loss of the melting endotherm of DTZ. The ionic interaction was confirmed by the accelerated release of DTZ from CAS containing formulations in dissolution media with high ionic strength indicative of an ion exchange process.