Rheological characterization of diltiazem HCl/cellulose wet masses using a mixer torque rheometer

The objective of the present investigations was to study the rheological behavior of wet powder masses containing two commonly used cellulose ethers, hydroxypropyl methylcellulose (HPMC) and hydroxyethyl cellulose (HEC), 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 both the cellulose ethers used for the study are water soluble, isopropyl alcohol (IPA) was used as the wet massing liquid. For comparison purposes. microcrystalline cellulose (MCC) was used as a reference material. In addition, pelletization studies of these powder formulations were carried out to establish a critical window of the wet massing liquid needed for successful extrusion/spheronization. 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 of wet masses of DTZ-MCC and DTZ-HEC systems were similar and indicated poor liquid spreading, poor substrate wetting and weak substrate/binder interaction, and exhibited a narrow window of tolerance for the wet massing liquid. In contrast, the rheological profiles of DTZ-HPMC system indicated that this powder system has relatively better liquid spreading, better substrate wetting and higher degree of substrate/binder interaction, and higher liquid retention capability. During pelletization, in contrast to the other two powder systems, the DTZ-HPMC system could be extruded/spheronized using a relatively wider range of IPA level in Nica(R) extruder/spheronizer without becoming over-wet, which concurs with the observations made from the mixer torque rheometer studies. The study concludes that with DTZ being the common component in the three powder systems, the critical liquid requirement of the three powder systems is a function of the individual cellulosic component of the system. Of the three cellulosic excipients, HPMC exhibited a relatively higher affinity for IPA and the ability to be extruded:spheronized successfully with a wider range of the liquid. (C) 1998 Published by Elsevier Science B.V. All rights reserved.