The role of fine excipient particles in adhesive mixtures for inhalation
Journal article, 2021

Despite the fact that adding fines improve the drug dispersion performance during inhalation, the scarcity of mechanistic insight into the formulation process, independent of the aerosolization, has kept the dispute on the underlying improvement mechanism open. We therefore simulate ternary formulations (carrier, drug, fines) in a vibrational cell to explore the mixing mechanism and the effect of particle size and loading ratio of fines on formulation performance. Results suggest that the buffer theory is a critical contributory mechanism since it curtails the carrier's collision rate and, therefore, decreases agglomerate breakage. Consequently, relatively larger drug aggregates are formed over the carrier, which eventually experiences greater detachment forces. A simple dispersion test is performed to evaluate drug detachment rate at wall-collision. An excess of cohesive fines, or using larger fines, diminishes the rotational kinetic energy of coarse particles by lumping them together. This reduces drug agglomerate breakage and leads to poor mixing.

agglomerate breakage

discrete element method

fine excipient particles

ternary formulation

adhesive mixing

Author

Mohammadreza Tamadondar

Chalmers, Chemistry and Chemical Engineering, Chemical Technology

Kian Salehi

Student at Chalmers

Per Abrahamsson

AFRY

Anders Rasmuson

Chalmers, Chemistry and Chemical Engineering, Chemical Technology

AICHE Journal

0001-1541 (ISSN) 1547-5905 (eISSN)

Vol. 67 5 e17150

Dry coating in dense particulate high-shear systems

Swedish Research Council (VR) (2014-4196), 2015-01-01 -- 2018-12-31.

Subject Categories

Pharmaceutical Sciences

Applied Mechanics

Biomaterials Science

DOI

10.1002/aic.17150

More information

Latest update

4/28/2021