Evaluation of alternative methods to derive particle density from compression data

Abstract

The determination of particle density is a critical part of material characterization regarding compression analyses. Helium pycnometry as the most commonly used method is criticized for different aspects. Most prominent is the susceptibility to errors when measuring water-containing powders. Alternative methods for determining particle density using compression data have already been described. However, a systematic investigation and evaluation is still missing. In this study, the methods by Sun and Krumme were investigated in detail regarding their robustness against variations in tableting settings. Twelve pharmaceutical excipients were tableted at five different settings to verify the applicability and sensitivity to changes in the experimental set-up. Both methods were found to be robust against influencing parameters from the experiments. A sufficiently high compression pressure to approach a constant density value of the corresponding material during tableting was considered to be an essential requirement for the performance of the methods. Brittle materials with high yield pressure were found to be unsuitable for the application of both methods. The method of Krumme gave small deviations to measurements of helium pycnometry for water-free materials. By using the tablet density after in-die elastic recovery, Krumme's method could be used for water-containing materials as well. The method of Sun was found to give significantly smaller values for particle density due to inclusion of slow elastic recovery.