Determination of Physical and Chemical Stability in Pressurised Metered Dose Inhalers (MDIs): Potential New Techniques

The pressurised metered dose inhaler (pMDI) is one of the oldest and most commonly prescribed therapeutic systems for drug delivery to the lung. pMDIs are subject to rigorous physical and chemical stability tests during formulation and prior to commercial approval. Due to the time and cost associated with formulation and product development studies, there is a need, especially within an industrial setting, for novel techniques that allow fast screening of new formulations in terms of physical and chemical (physico-chemical) stability. The key problem with achieving this goal is in the nature of pMDI formulations. While conventional intravenous, oral and topical formulations are in a solid-state at STP, pMDIs are by their definition, pressurised, making the direct observation of physico-chemical properties in situ, difficult.

This review highlights the state-of-the-art techniques and physico-chemical characterisation tools that can potentially enhance the formulation and product development process for pMDIs. Techniques investigated include: laser diffraction, Raman spectroscopy, isothermal ampoule calorimetry, titration calorimetry and gas perfusion calorimetry. These are discussed in the context of pharmaceutical development, with a focus on their use for the determination of the physical and chemical stability in pMDI delivery systems. The operational principles behind each technique are briefly discussed and complemented with examples from the literature. The strengths and weaknesses of the above techniques are highlighted with the purpose of guiding the reader to identify the most promising technique.