A theoretical and experimental analysis of formulation and device parameters affecting solution MDI size distributions.

The influence of formulation and device configurations on the initial droplet and residual particle size distribution from solution MDIs was theoretically and experimentally examined. Aerodynamic size distribution tests were conducted to characterize the size distribution of the residual particles formed when a solution MDI is actuated. The measured size distributions were approximately log-normally distributed, and did not show evidence of a secondary large particle mode. Theoretical relationships were developed to relate the residual particle size distribution to the initial size distribution of the atomized droplets. The residual particle size distribution was shown to be proportional to the nonvolatile concentration to the one-third power. Ethanol concentration, propellant type, valve size, and actuator orifice diameter were all shown to affect the initial droplet size distribution. Deposition of drug in the mouthpiece and USP inlet affect the measured size distribution during aerodynamic particle size measurements. Although there is a significant increase in the size of initial droplets as ethanol concentration increases, there is only a minor increase in the size of the residual particles measured when the USP Inlet is used due to size dependent deposition in the USP inlet and actuator mouthpiece. Vapor pressure was shown to explain only part of the differences in the size of the atomized droplets for various formulations. Theoretical and empirical equations were developed that make it possible to predict the residual particle size distribution for solution MDIs. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2158-2175, 2004