Shear and flow behavior of pharmaceutical blends - Method comparison study

A method comparison study was undertaken to characterize the effects of the formulation composition on the flow and shear properties of pharmaceutically relevant powders. Fourteen blends with various concentrations of an active ingredient, magnesium stearate as a lubricant and silica as a glidant were prepared. These blends were characterized with two very different techniques: the gravitational displacement rheometer (GDR), and a rotational shear cell. The values of GDR flow index were compared to the values of principal stresses and cohesion obtained with the shear cell. These measurements are different in that the GDR operates in the gravity-driven flow regime while the shear cell utilizes an imposed normal force, which leads to a much more pronounced powder consolidation. In spite of these differences, the study demonstrated a significant correlation between the two methods, although some discrepancies were observed due to differences in the consolidation state for each technique. This observation was confirmed by measuring compressibility of these formulations with the FT4 Powder Rheometer; the presence of a cohesive component influenced the values of the shear cell principal stresses (and therefore, the shear cell flow factor) in a non-linear manner, contributing to the discrepancies in the correlation between the flow factor and the GDR flow index. Conversely, the correlation between the shear cell cohesion parameter and the GDR flow index was significantly better, as both indices test the materials at similar degree of consolidation. The study examined the limits and the ranges of applicability of each technique, offered recommendations on applications, where the use of each method was more reliable, as well as provided reasons for the methods' failure.