Improvement of a pharmaceutical powder mixing process in a tote blender via DEM simulations.

An industrial-scale pharmaceutical powder blending process was studied via discrete element method (DEM) simulations. A DEM model of two active pharmaceutical ingredient (API) components and a combined excipient component was calibrated by matching the simulated response in a dynamic angle of repose tester to the experimentally observed response. A simulation of the 25-minute bin blending process predicted inhomogeneous API distributions along the rotation axis of the blending container.

Carrier particle emission and dispersion in transient CFD-DEM simulations of a capsule-based DPI.

The dispersion of carrier-based formulations in capsule-based dry powder inhalers depends on several factors, including the patient's inhalation profile and the motion of capsule within the device. In the present study, coupled computational fluid dynamics and discrete element method simulations of a polydisperse cohesive lactose carrier in an Aerolizer® inhaler were conducted at a constant flow rate of 100 L/min and considering an inhalation profile of asthmatic children between 5 and 17 years approximated from literature data. In relevant high-speed photography experiments, it was observed that the powder was distributed to both capsule ends before being ejected from the capsule.

Estimating inter-patient variability of dispersion in dry powder inhalers using CFD-DEM simulations.

Drug delivery from a capsule-based dry powder inhaler depends on the inhaler's design, the drug's formulation, and the inhalation maneuver. The latter affects both the air flow and the capsule motion in the inhaler. It is well known that patient-to-patient variability is a major challenge in the design of new inhaler types.

Understanding the motion of hard-shell capsules in dry powder inhalers.

The delivery of small drug particles from a dry powder inhaler (DPI) into the patient's peripheral airways requires the dispersion of the powder. In DPIs that contain a rotating pierced capsule, the capsule's motion is paramount to powder dispersion. Previous studies have simplified the capsule motion in an Aerolizer® inhaler as a constant rotation around a fixed center.