Optimizing the development and analysis of solution based metered dose inhalers

Abstract

The current work focuses on the development and evaluation of techniques and models that can facilitate the development of solution based metered dose inhalers. These include an online reverse phase hplc method for analyte quantitation from propellant based pressurized metered dose inhalers. The technique ( direct injection method) finds applications in determining solubility of compounds in aerosol propellants and can possibly be used for stability analysis. With the development of this technique it would be feasible to generate a solubility database in order to understand the physico-chemical factors affecting the solubility and also possibly predict the solubility of compounds in HFA 134a propellant. The regular solution theory based on solubility parameter approach was evaluated for this purpose by utilizing a set of 35 diverse compounds in HFA 134a. A new product performance evaluation tool; the Model 3320 series Aerodynamic Particle Sizer (APS) used in conjunction with Model 3320 Impactor Inlet was evaluated for analysis of solution metered dose inhalers. The Model 3320 APS series provides rapid aerodynamic size distribution data and coupled with Model 3306 Impactor Inlet allows for the chemical analysis of the Inlet port, 'respirable' mass and 'non-respirable' mass. It was shown that in order to obtain comparable results between the Model 3306 Impactor Inlet and the Andersen Cascade Impactor (ACI), an extension to the USP throat may be necessary. The solubility data generated by the direct injection method coupled with the 'respirable deposition' data generated using the APS 3320 series can be used to optimize the product performance of cosolvent based solution metered dose inhalers.