True density is commonly measured
using helium pycnometry. However, most water-containing powders, for example,
hydrates, amorphous drugs and excipients, and most tablet formulations, release
water when exposed to a dry helium atmosphere. Because released water brings
significant errors to the measured true density and drying alters the nature of
water-containing solids, the helium pycnometry is not suitable for those
substances. To overcome this problem, a novel method has been developed to
accurately calculate powder true density from compaction data. No drying
treatment of powder samples is required. Consequently, the true density thus
obtained is relevant to tableting characterization studies because no
alteration to the solid is induced by drying. This method involves nonlinear
regression of compaction pressure-tablet density data based on a modified
Heckel equation. When true density values of water-free powders derived by this
novel method were plotted against values measured using pycnometry, a
regression line with slope close to unity and intercept close to zero was
obtained. Thus, the validity of this method was supported. Using this new
method, it was further demonstrated that helium pycnometry always overestimates
true densities of water containing powders, for example, hydrates,
microcrystalline cellulose (MCC), and tablet formulations. The calculated truedensities of powders were the same for different particle shapes and sizes of
each material. This further suggests that true density values calculated using
this novel method are characteristic of given materials and independent of
particulate properties.
Copyright
2004 Wiley-Liss, Inc. and the American Pharmacists Association
