Study of effect of excipient source variation on rheological behavior of diltiazem HCl-HPMC wet masses using a mixer torque rheometer

Abstract

In the wet massing of powders and powder blends, the rheological behavior of the wet powder masses not only plays a critical role in the unit process but also influences the attributes of the product. The physical properties of the powder excipients, such as particle size and size distribution, shape, surface area, bulk and tapped density and surface morphology, are a major source of variability in the rheological behavior of wet powder masses and the quality attributes of the final product. The objective of the present investigations was to study the rheological behavior of wet masses containing hydroxypropyl methylcellulose (HPMC) obtained from two sources (Methocel® from Dow and Pharmacoat® from Shin-Etsu) using a mixer torque rheometer. In order to simulate a real formulation, diltiazem HCl (DTZ) (40% loading) was used as part of the substrate powder mass. Hydroxypropyl cellulose (HPC) was used as the binder. Since HPMC is water-soluble, isopropyl alcohol (IPA) was used as the wet massing liquid. The rheological behavior of the wet powder masses was studied as a function of mixing time and amount of wet massing liquid (IPA). The rheological profiles obtained for DTZ-Methocel and DTZ-Pharmacoat exhibited same magnitude for mean torque, however, for DTZ-Pharmacoat the peak was more extended than that for DTZ-Methocel. The extended peak for DTZ-Pharmacoat indicated that the wet mass will stay suitable during the process for larger quantities of the wet massing liquid before turning into paste and becoming unsuitable for the process as compared with the DTZ-Methocel system. The mixing kinetics of the two powder systems appeared to be quite different. These differences in the rheological behavior of the wet masses may be attributed to the difference in the particulate and surface properties of the two HPMCs. Some of the properties of the two HPMCs, such as particle size and size distribution, surface area, surface morphology and DSC thermograms, explain the difference observed in their rheological behavior. The difference in the rheological profiles of the two DTZ-HPMC systems indicated superiority of Pharmacoat over Methocel considering their wet massing behavior.