Summary

The use of the Next Generation Impactor (NGI) to measure the aerodynamic particle size distribution of Dry Powder Inhalers (DPI) is a well-established technique that allows quantification of Active Pharmaceutical Ingredient (API) present in the respirable fraction <10 µm. Quantification is typically performed via chemical assay (e.g. HPLC).

Morphologically-Directed Raman Spectroscopy (MDRS, performed using the Morphologi 4-ID by Malvern Panalytical) can be used to characterise particles to evaluate morphological differences between API and excipients. As well as providing a different method to the NGI to measure the particle size of individual APIs in dual (or triple) therapy DPI products, qualitative information can also be understood from the Raman chemical identification and will highlight the presence and composition of agglomerates ^[1].

This is something that cannot be inferred solely from impactor data but will provide hugely important information as to the way the product may behave in-vivo. The number and composition of agglomerates (i.e. whether they are drug-drug, drug-excipient or a combination of these) will ultimately influence dissolution behaviour.

Key Message

NGI and MDRS can be used as orthogonal methodologies in measuring drug particle size and agglomerate species in combination Dry Powder Inhaler (DPI) formulations. This is advantageous to all DPI developers but has particular relevance to generic developers hoping to match deposition and dissolution behaviour against a reference product.