Characteristics of multi-component formulation granules formed using distributive mixing elements in twin screw granulation.

This work examines the influence of pharmaceutical powder formulation characteristics on granule properties formed using distributive mixing elements (DMEs) in twin screw granulation. High and low drug dose formulations with three different active pharmaceutical ingredients (APIs) were considered. The type and concentration of the API in the formulation significantly affected the dry blend particle size distribution and the wet blend dynamic yield strength. However, despite the differences in blend properties, the granule size distributions were not significantly affected by the type of API used. The granule size distributions were solely the functions of the liquid-to-solid ratio and screw element geometry. However, the granule porosities were observed to be dependent on both the liquid-to-solid ratio and the dynamic yield strength of the blends. This work is the first to study the influence of drug loading and API type on the granule attributes produced using distributive mixing elements.

Capsule-Based dry powder inhaler evaluation using CFD-DEM simulations and next generation impactor data.

Capsule-based, single-dose dry powder inhalers (DPIs) are commonly-used devices to deliver medications to the lungs. This work evaluates the effect of the drug/excipient adhesive bonding and the DPI resistances on the aerosol performance using a combination of empirical multi-stage impactor data and a fully-coupled computational fluid dynamics (CFD) and discrete element method (DEM) model. Model-predicted quantities show that the primary modes of powder dispersion are a function of the device resistance. Lowering the device resistance increases its capacity to transport a wider range of particle size classes toward the outlet and generate more intense turbulence upstream therein. On the other hand, a higher device resistance increases the velocity of the tangential airflow along the device walls, which in turn increases the intensity of particle/device impaction. Correlating model data and experimental results shows that these differing powder dispersion mechanisms affect different formulations differently, with finer aerosols tending to result when pairing a lower resistance device with formulations that exhibit low API/excipient adhesion, or when pairing a high resistance device with more cohesive formulations.

Stress results from two-dimensional granular shear flow simulations using various collision models.

Collision resolution is one of the key elements in a discrete element method algorithm for modeling granular flows. Several collision models have been proposed for this process. The hard-particle collision approach is typically used for dilute systems, or for those in which the assumption of binary and instantaneous particle-particle contact remains valid. As the solids fraction increases, however, multiple, enduring collisions can occur and a soft-particle approach is more appropriate for resolving the collision dynamics. In this work, the delineation between dilute and dense systems and the suitability of contact models are explored for a range of solid fractions. Stress results for two-dimensional shear flow simulations are compared using several collision models including an event-driven hard-particle model, a hysteretic spring soft-particle collision model following Walton and Braun [J. Rheol. 30, 949 (1986)], and a hybrid hard-particle-with-overlap model following Hopkins and Louge [Phys. Fluids A 3, 47 (1991)]. Results show that stresses are accurately predicted for a range of solids fractions, coefficients of restitution, and friction coefficients by both the hard-particle-with-overlap and soft-particle models so long as a sufficiently large loading stiffness is used for the soft-particle model. Additional results investigating the accuracy of the collision models and the amount of collisional overlap are presented as functions of the simulation time step and model parameters.