A Novel Method for Deriving True Density of Pharmaceutical Solids Including Hydrates and Water-Containing Powders

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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 true densities 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.

Original languageEnglish (US)
Pages (from-to)646-653
Number of pages8
JournalJournal of Pharmaceutical Sciences
Issue number3
StatePublished - Mar 2004

Bibliographical note

Copyright 2017 Elsevier B.V., All rights reserved.


  • Modified Heckel equation
  • Nonlinear regression
  • Porosity
  • Tableting
  • True density

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