(598c) Study of the Flow Performance and Physical Properties of a New Direct-Compression (DC) Grade of HPMC and How Its Performance and Attributes Compare to Those of the Existing Methocel(TM) CR Grades

The purpose of this study was to investigate the flow performance and physical properties of a new direct-compression (DC) grade of HPMC designed to streamline manufacture of matrix tablets and how its performance and attributes compare to those of the existing METHOCEL^TMCR grade.

Multiple lots of the improved DC material and METHOCEL CR were characterized via bulk powder flow, particle size and shape analysis, bulk/tapped density, sieve separation, and powder avalanche testing. In addition, a 2-kg sample from each lot of HPMC powder was tumbled in a V-blender for 10 minutes, and powder aliquots were subsequently collected at three depths (surface, 7-10 cm, and 18 cm below surface). Each of the aliquots was then characterized via QICPIC analysis (Dynamic Image Analysis DIA system QICPIC^TM). Finally, characterization of each powder was attempted using an internally developed powder flow test, found to be discriminatory from one morphology to another and indicative of powder flow through an industrial hopper.

Where the improved DC material was successfully characterized within the powder flow apparatus, METHOCEL CR rat-holed and plugged the apparatus, which had to be tapped from the outside to clear the CR material. Although K100M grades generally exhibited higher Carr indices than the corresponding K4M grades, the DC materials consistently exhibited lower Carr Indices than METHOCEL CR, regardless of molecular weight grade.  Mean times between powder avalanches were lower for the DC materials as well. Upon separation through a 63-µm sieve, the fines content was lower in the DC material (<50% vs. >60% passed through). Both scanning electron microscopy and QICPIC analysis confirmed the presence of granular, more spherical particles in the DC material. There was no sign of segregation of DC particles after tumbling for 10 min.

Because the DC material is more granular and has a more spherical morphology, this material is more flowable and facilitates direct compression. Furthermore, a complementary paper will demonstrate the utility of the DC material in a dry granulation process to manufacture matrix tablets containing an active pharmaceutical ingredient and commonly utilized excipients. Both sets of findings will assist formulators in choosing the morphology grade of HPMC best for their standard tablet manufacturing processes.

Copyright American Association of Pharmaceutical Scientists