Impact of high shear blending on distribution of magnesium stearate on lactose for dry powder inhaled formulations.

The use of magnesium stearate along with lactose in Dry Powder Inhaler (DPI) formulations is increasing. The impact of different conditions of high shear blending on the distribution of magnesium stearate on lactose particles was investigated in this study. The formulated blends were manufactured using high shear blending of pre-blended coarse and fine lactose particles with 1.0% (w/w) magnesium stearate under different blending conditions, specifically blending speed and time. The effects of blending conditions on the distribution of magnesium stearate on lactose particles were clearly identifiable by characterizing the formulated blends by means of rheological evaluations, scanning electron microscopy, and chemical surface analysis using time-of-flight secondary ion mass spectrometry (ToF-SIMS). Rheological properties were significantly affected in blends with magnesium stearate compared to blends without magnesium stearate. Blending speed exhibited a strong influence on the distribution of magnesium stearate on lactose surface, while blending time had relatively minor effect.

Micro-macro correlations and anisotropy in granular assemblies under uniaxial loading and unloading.

The influence of contact friction on the behavior of dense, polydisperse granular assemblies under uniaxial (oedometric) loading and unloading deformation is studied using discrete element simulations. Even though the uniaxial deformation protocol is one of the "simplest" element tests possible, the evolution of the structural anisotropy necessitates its careful analysis and understanding, since it is the source of interesting and unexpected observations. On the macroscopic, homogenized, continuum scale, the deviatoric stress ratio and the deviatoric fabric, i.e., the microstructure behave in a different fashion during uniaxial loading and unloading. The maximal stress ratio and strain increase with increasing contact friction. In contrast, the deviatoric fabric reaches its maximum at a unique strain level independent of friction, with the maximal value decreasing with friction. For unloading, both stress and fabric respond to unloading strain with a friction-dependent delay but at different strains. On the micro-level, a friction-dependent non-symmetry of the proportion of weak (strong) and sliding (sticking) contacts with respect to the total contacts during loading and unloading is observed. Coupled to this, from the directional probability distribution, the "memory" and history-dependent behavior of granular systems is confirmed. Surprisingly, while a rank-2 tensor is sufficient to describe the evolution of the normal force directions, a sixth order harmonic approximation is necessary to describe the probability distribution of contacts, tangential force, and mobilized friction. We conclude that the simple uniaxial deformation activates microscopic phenomena not only in the active Cartesian directions, but also at intermediate orientations, with the tilt angle being dependent on friction, so that this microstructural features cause the interesting, nontrivial macroscopic behavior.