Laboratory methods for assessing API sensitivity to mechanical stress during agitated drying

Abstract Two distinct laboratory methods have been developed to assess the propensity of active pharmaceutical ingredients to undergo particle breakage during agitated drying operations. In the first method, mechanical stress is applied to particles by mechanical agitation of powders compressed under an applied normal force. For the second, particles experience stresses as they are carried within a pressurized gas stream. These methods are simple, relatively compound-sparing, and are used to rank materials according to a quantitative breakage classification scale as hard, medium, or easy to break. Based on the results obtained using these methods at laboratory scale, recommendations and precautions for processing at larger scale are made. In this paper, these methods are described in detail, and the results, obtained for several pharmaceutical compounds, are presented.