By Paul Kippax, Product Group Manager, Malvern Instruments
Optimizing a dry powder inhaler (DPI) to achieve the desired emitted dose and aerodynamic particle size distribution (APSD) can be made significantly faster and easier by using data acquired by laser diffraction and morphologically directed Raman spectroscopy (MDRS) as a supplement to cascade impaction data.
All OINDP developers know that DPIs pose special challenges due to the number of variables that can affect the amount of API delivered to the lung — properties such as powder flowability and cohesion, patient lung capacity, inhalation strength and technique, and the design of the device, including its internal resistance — so that blindly changing formulation and device variables to achieve desired aerosolization properties can result in a lengthy and costly development program.
While there is no disputing the central role of cascade impaction in DPI characterization, gaining understanding and control of the dynamic aerosolization and dispersion processes that occur during device use is key to the development process, and cascade impaction measures only what happens after aerosolization. In other words, cascade impaction measures the aerodynamic particle size distribution (APSD) of the emitted dose but sheds no light on how that dose was emitted. In addition, the use of HPLC for analysis of cascade impactor samples effectively destroys the sample, causing any information on the form or state of agglomeration of the sample, and the knowledge this may provide regarding dispersion of the dose, to be lost.
For DPIs, unlike nasal sprays and some inhalation solutions, there is no regulatory requirement for the use of laser diffraction; but laser diffraction’s ability to look at how the aerosol is emitted from the inhaler in real time can be particularly enlightening, especially in formulations where one or more APIs must separate from the carrier for effective delivery.
With MDRS, which can differentiate the chemical composition of different particles in addition to measuring particle size and shape, developers can quickly and easily determine the number and type of agglomerates remaining after aerosolization for a wide range of conditions.
