Influence of Micronization Method on the Performance of a Suspension Triamcinolone Acetonide Pressurized Metered-Dose Inhaler Formulation

Abstract

The purpose of this study was to investigate the influence of micronization technique on performance and stability of the model drug formulated in a suspension-based pressurized metered-dose inhaler (pMDI). The model drug, triamcinolone acetonide (TAA), was subjected to ball milling or air-jet milling prior to formulation of the pMDI. The dose delivery characteristics of the emitted aerosol cloud were monitored for the ball-milled, air-jet-milled, and unmicronized TAA pMDI formulations prior to and after storage at 25 and 40°C. Cascade impaction was used to determine the aerodynamic particle size distribution of the emitted dose. Both micronization techniques reduced the drug particle size distribution and the polydispersity of the drug particles to a similar extent, but the ball-milling technique reduced the crystallinity of the drug to a greater degree compared to the air-jet-milling technique. The air-jet-milled and unmicronized TAA pMDI displayed similar aerodynamic particle size distributions of the emitted aerosol and respirable fractions over the storage period. The ball-milled TAA resulted in a pMDI formulation with the smallest aerodynamically sized particles and the highest respirable fraction compared to the air-jet-milled or unmicronized TAA pMDI formulations. The micronization techniques significantly influenced the dose delivery characteristics as a result of different initial particle size distributions, amorphous contents, and surface energies.