Fluidised Powder Blending to Control Particle-Particle Interaction – The Future of DPI Formulation

Afzal Mohammed¹, Jasdip Koner², Olaitan Abiona¹ & David Wyatt¹,²

¹Aston University, Aston Triangle, Birmingham, B4 7ET, United Kingdom

²Aston Particle Technologies Ltd, Aston University, Aston Triangle, Birmingham, B4 7ET, United Kingdom

Summary

Traditional blending processes for dry powder inhaler (DPI) manufacture involve use of equipment that relies upon the solid-solid mixing of powders to deagglomerate and disperse cohesive micronised active pharmaceutical ingredients (APIs) onto the surface of coarser carrier particles, which often generate mechanical shear and are generally inefficient. Researchers at Aston University have developed a novel dry coating process which avoids the limitations of solid-solid blending by micro-fluidising powders held at the surface of a rotating chamber by a strong centrifugal field (high G) through the application of a nitrogen air-blade. Cohesive API is dispersed into primary particles in the fluidised state and coated onto the surface of much larger co-fluidised lactose particles. In a model study, cohesive micronised Rhodamine B was coated onto an inhalation grade lactose to mimic a typical DPI formulation. Blends were manufactured under a range of different processing conditions and the time course of the coating process was studied using confocal microscopy and scanning electron microscopy. This work exposed the nature of the coating process and the transitions through which the fine particles pass to achieve efficient coating. In a further study, a genuine DPI formulation, micronised fluticasone propionate was coated onto lactose (at 0.71%^w/_w) following a design of experiment scheme. The results demonstrate how the technology can control the formulation of DPI blends through manipulation the three process parameters; process speed, air-flow rate and process time. Two-dimensional response maps at set processing times were constructed highlighting how the critical process parameters of the novel methodology control two blend responses, content uniformity and fine particle fraction performance, and illuminate a standard to which DPI performance of the future might be designed and controlled.