The analysis and prediction of functional robustness of inhaler devices.

Abstract

The studies described in this paper were undertaken to develop a method for the quick analysis and prediction of robustness of inhaler devices, and to define a standard among inhaler devices against which the structural integrity of new innovations could be judged. In addition, an effort was made to correlate mechanical properties with product performance metrics. The effect of mechanical stresses, alone and in combination with elevated temperatures, on the in vitro performance of pressurized metered dose inhalers (pMDIs) was investigated. The innovator pMDI devices (Ventolin HFA, GlaxoSmithKline) tested proved to be functionally robust in response to extreme mechanical stresses, suggesting that they are appropriate standards on which acceptance criteria for new devices should be defined. The actuator seat where the valve stem is inserted was identified as the critical area of the pMDI. A comparison of innovator vs. generic albuterol MDIs revealed that generic products approved as "equivalent " to the innovator products by current standards are not necessarily equivalent in ruggedness. Finite-element models of the actuator seat of Ventolin HFA (polypropylene) and QVAR 40 (high-density polyethylene) (3M Healthcare Ltd.) capable of predicting mechanical failure of MDIs were established. The material properties as well as the actuator design influenced the operational limit of MDIs. Stress analysis using finite-element modeling could be effectively used for the selection of the optimal design and appropriate materials of construction, which could lead to the development of robust inhalers while shortening the product development cycle.