We describe a new instrument and method for measuring compressed bulk density of respirable pharmaceutical powders under low compression pressure: the modulated compression tester. The instrument modulates compression and decompression steps, allowing scrutiny of the overall compression response of samples. Compared to established methods for the determination of density and related parameters for pharmaceutical powders, this instrument has the capability of measuring smaller samples. The relative humidity can also be controlled in the instrument (3 % to 95 % RH), allowing assessment of the effect of moisture on compression response. We have used the instrument to determine the compressed bulk density of Trehalose, Leucine, Trileucine, and Mannitol powders of varying crystalline and amorphous compositions and particle size and size distribution, demonstrating that the new modulated compression tester is suitable for low pressure (< 1200 kPa) density measurement of respirable powders (< 10 μm) and expensive active pharmaceutical ingredients available in limited quantities (typical sample mass requirement of < 100 mg). In addition, the modulation feature of the instrument allows the analysis of the transition from plastic to semi-elastic compression response. The outputs and features of this instrument are useful for formulation development, quality control measurements, discerning between different or similar powders due to differences in the compression response, and optimizing powder compression parameters for pharmaceutical applications.
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