Compression Analysis of Pharmaceutical Powders : Assessment of Mechanical Properties and Tablet Manufacturability Prediction

The papers of this thesis are not available in Munin: <br/>1. Nordström, J., I. Klevan and G. Alderborn: 'A particle rearrangement index based on the Kawakita powder compression equation', Journal of Pharmaceutical Sciences (2009) 98(3): 1053-1063. Available at <a href=http://dx.doi.org/10.1002/jps.21488>http://dx.doi.org/10.1002/jps.21488</a> <br/>2. Klevan, I., J. Nordström, A. Bauer-Brandl, and G. Alderborn: 'On the physical interpretation of the initial bending of a Shapiro-Konopicky-Heckel compression profile', European Journal of Pharmaceutics and Biopharmaceutics (2009) 71(2): 395-401. Available at <a href=http://dx.doi.org/10.1016/j.ejpb.2008.09.014>http://dx.doi.org/10.1016/j.ejpb.2008.09.014</a> <br/>3. Klevan, I, J. Nordström, I. Tho and G. Alderborn: 'A statistical approach to evaluate the potential use of compression parameters for classification of pharmaceutical powder materials', European Journal of Pharmaceutics and Biopharmaceutics (2010) 75(3): 425-435. Available at <a href=http://dx.doi.org/10.1016/j.ejpb.2010.04.006>http://dx.doi.org/10.1016/j.ejpb.2010.04.006</a> <br/>4. Nordström, J., Klevan, I. and G. Alderborn: 'A protocol for the classification of powder compression characteristics' (in press at European Journal of Pharmaceutics and Biopharmaceutic) <br/>5. Klevan, I, Alderborn, G and A. Bauer-Brandl: 'Prediction of tablet manufacturability from compression parameters: a basic study using simple model materials' (manuscript)Although the tablet has been produced in large quantities for a long time, there is a need for better understanding of the manufacturing process. This thesis deals with compression analysis for assessment of mechanical properties and tablet manufacturability prediction. The goal was to increase the understanding of the response in the powder material during the tableting process. For this purpose, compression testing of powder material was conducted. This method allows for poorly compacted materials to be studied, but the critical point is the physical interpretation of the compression parameters derived. Therefore, the first part of the thesis deals with investigation of the interpretation of parameters from the Kawakita and Shapiro- model. It was found that a combination of the Kawakita a and b-1 parameters into an ab- index could reflect the incidence of particle rearrangement. Furthermore, it was found that for materials showing low degree of particle rearrangement, the initial curvature in a Heckel profile was a reflection of the degree of particle fragmentation, described mathematically by the Shapiro f parameter. In addition, the deformability of the particles could be assessed by the Heckel yield pressure. These three descriptors were combined into a classification system which was challenged by compression analysis of a large set of pharmaceutically relevant materials. The results indicated that a sequential approach was effective for assessment of mechanical properties and a description of this in the form of a protocol was suggested. Furthermore, the tableting relevant information found in compression data was evaluated by multivariate calibration. The Kawakita a parameter was the only compression parameter able to point towards the resulting tablet strength. The results further indicated that the Kawakita b-1 parameter corresponded to the pressure needed to initiate deformation of the bulk and hence needed to produce a coherent tablet. This thesis presents a protocol for the assessment of mechanical properties of pharmaceutical powders, and evaluates the tableting relevant information brought forward by compression data. This could be useful in a formulation development phase, enhance process understanding and possible also be applicable for monitoring of the tableting process