Evaluation of alternative methods to derive particle density from compression data.

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.

Multivariate data analysis to evaluate commonly used compression descriptors.

Numerous studies elucidated material behavior based on compression analyses. Especially compressibility, compactibility and tabletability were in the focus of these investigations. In the present study, a comprehensive multivariate data analysis was performed using principal component analysis method. Twelve pharmaceutically used excipients were selected for direct compression tableting and subsequent evaluation of several compression analyses. Material properties, tablet properties, tableting parameters and parameters from compression analyses were used as input variables. The materials could successfully be grouped using principal component analysis. Of the tableting parameters, the compression pressure showed the greatest influence on the results. The tabletability was found to be the most important compression analysis in the material characterization. Compressibility and compactibility only played a minor role in the evaluation. Some important insights have been gained for a deeper understanding of the tableting process using the multivariate approach to evaluate the variety of compression data.

Functionality of disintegrants with different mechanisms after roll compaction.

The aim of this study was to investigate the functionality of two disintegrants (crospovidone and croscarmellose sodium) in tablet formulations processed via roll compaction and subsequent tableting. The influence of different fillers and the effect of sodium lauryl sulfate on the disintegration process were studied using full factorial design. For a direct comparison of disintegrant functionality, the center point formulations were manufactured via direct compression. Tablet characteristics, such as tensile strength, solid fraction, disintegration time and mechanism, and dissolution profile were determined. The results allow the conclusion that the functionality of the disintegrants is impaired by dry granulation. Both the disintegration mechanism and the disintegration time were different when comparing tablets made after dry granulation and by direct compression. The effect was more pronounced on the functionality of crospovidone than on that of croscarmellose sodium. In addition, sodium lauryl sulfate showed a notable influence on all tablet properties due to its lubricating effect. The variation of the filler also had a remarkable effect on the tablet characteristics. The results link excipient functionality to drug product properties depending on the applied manufacturing process and could contribute to extend the Manufacturing Classification System to excipient characteristics.