Use of 3D Printing Technology to Investigate Particle Adhesion and Air Entrainment in a DPI System

Abstract

Advanced mathematical models exist for the adhesion and detachment of particles from surfaces, either as single particles or multilayers. In Dry Powder Inhaler (DPI) systems for inhalation, blending of small micronized particles with a larger carrier is critical to ensure blend uniformity and dose consistency (adhesion). Conversely, when the patient comes to use their DPI, the force balance requirement changes and particle detachment drives the performance of the product and therapeutic effect by allowing particles to penetrate into the lungs. Understanding particle adhesion and detachment is critical. Particle size and shape, environmental humidity, surface chemistry and surface roughness all have an impact on the adhesion and ultimate entrainment of particles.

In this work, novel microscopic scale surfaces were produced using advanced 3D printing technology (dual photon polymerisation) representative in size to a lactose carrier particle. A bespoke rig was constructed for the controlled aerosolization of particles in an airstream and particle detachment was recorded by air titration experiments. SEM and Raman technology were used to calculate particle detachment at different air flows. The greater the airflow velocity hitting the structure, the more micronized particles were detached from the 3D printed surfaces and entrained. The designed roughness of the 3D printed substrate surface was critical in determining particle detachment or retention in an airstream and this was analysed by atomic force microscopy (AFM).

Microstructure roughness smaller than the diameter of the particle of interest was able to promote particle detachment consistent with the Rock’n’Roll particle resuspension theory however too high a surface roughness allowed mechanical interlocking of particles to occur. In these instances, particle detachment was poor and high adhesion zones were formed.

Finally, Raman particle mapping technology was used to observe the dispersion of two commercially available micronized APIs across a DPI carrier particle using different powder blending techniques

Date of Award	4 Nov 2020
Original language	English
Awarding Institution	University of Bath
Sponsors	Chiesi Limited
Supervisor	Robert Price (Supervisor), Paul De Bank (Supervisor) & Ian Blagbrough (Supervisor)