(18a) Combination of Experimental and Mathematical Techniques for Characterization of Particle Friability

This work involves the development of methodology for characterizing and predicting the friability of granules by combining experimental and theoretical techniques as an extension of our recent work [1]. First, experimental data of granule attrition are collected via a bench-top SYMPATEC laser diffraction particle size analyzer and HELOS dry particle disperser. Samples are analyzed at different inlet air pressures of 0.3 to 6.0 bar. The key part of the HELOS disperser (which can be considered a pneumatic conveying system) mostly responsible for attrition is the bend between the inlet and the laser diffraction measurement chamber. It is generally recognized that the particles during pneumatic conveying experience extensive impact loads at the bends because of collisions with the bend walls. Increasing the inlet air pressure produce a finer PSD as a consequence of more extensive attrition. Second, a simple plug flow population balance (PF-PB) mathematical model of breakage is developed. The model is solved using the Quadrature Method of Moments (QMOM) and used for preliminary evaluation of the breakage rate properties by fitting a model to experimental data from the SYMPATEC equipment. Different semi-empirical expressions for the breakage kernels and for the daughter distribution functions are tested. Multiple breakage distribution functions, proposed by Diemer and Olson [2], are usually needed to get satisfactory agreement with experimental data. Finally, a model combining CFD and QMOM methodologies is developed. The combined model uses the function forms for the breakage kernel and for the daughter distribution function obtained before using the PF-PB model. However, the detailed CFD-PB model also allows us to relate the breakage kernel parameters to particular flow properties. It was found that for a given experimental set-up with diluted gas-solid flow, that the breakage rate of granules is proportional to the characteristic particle size and to the square of the impact velocity between a granule and the equipment wall, and can be expressed using the form proposed by Moreno-Atanasio and Ghadiri [3]. The combined experimental and theoretical methodology was tested for evaluation of the breakage rate parameters of different granules. The methodology requires small quantities (~ 20g) of granules, which is particularly useful for comparison of different formulations during the drug development process. Moreover, physically based models calibrated by the above methodology and combining properties of the gas-solid flow with the PB models can also be employed to predict attrition in manufacture-scale pneumatic conveying systems.

[1] P. Rajniak, K. Dhanasekharan, C. Sinka, N. MacPhail, R. Chern, S. Fitzpatrick, Modeling and measurement of granule friability, Conference Proceedings CD Vol.2, Fifth World Congress on Particle Technology, 23-27 April 2006, Orlando, FL, USA. [2] R. B. Diemer, J. H. Olson, A moment methodology for coagulation and breakage problems: Part3 ? generalized daughter distribution functions, Chem. Eng. Sci. 57 (2002) 4187 ? 4198. [3] R. Moreno-Atanasio, M. Ghadiri, Mechanistic analysis and computer simulation of impact breakage of agglomerates: Effect of surface energy, Chem. Eng. Sci. 61 (2006) 2476 ? 2481.