Investigating the microstructure of dry powder inhalers using orthogonal analytical approaches   

Gonçalo Farias¹, William Ganley¹, Debbie Huck-Jones², Paul Kippax², Jagdeep Shur¹ & Robert Price¹

¹Department of Pharmacy and Pharmacology, University of Bath, UK.

²Malvern Instruments Limited, Grovewood Road, Malvern, UK.

Summary

With several patent expirations of innovator DPI products looming, the major challenge for generic entry is understanding and demonstrating bioequivalence (BE) with respect to the innovator reference product. BE of locally acting drugs has been a long-standing challenge for the introduction of generic DPI drug products, which do not rely on the systemic circulation for targeting the site of action. The FDA has conceived a concept for demonstrating BE of topical products, which is called Q3-equivalence. This term describes structural similarity between test and reference product and refers to the arrangement of matter and state of aggregation of the product. However, demonstrating Q3-equivalence between test and reference DPI products is challenging due to the complexity of DPI dosage forms. Therefore, there is a requirement of in-vitro analytical tools that maybe employed orthogonally to demonstrate Q3-equivalence of the microstructure of test and reference DPI drug products.

The differences in the physical microstructure of a formulated DPI blend may not only impact the aerosol dispersion performance within a device but could also affect other factors within the lung. Hence, investigations into the state of aggregation for the resulting arrangement of the dispersed dose could be vitally important in demonstrating structural similarity and BE between DPI products.

Our proposed approach utilizes a combination of orthogonal techniques to support characterization of DPI formulations. These techniques include morphology directed Raman spectroscopy (MDRS) and UniDose-enabled dissolution testing. In this study, we have investigated the microstructure of the aerosolised dose of Seretide and Advair DPIs using UniDose and MDRS.