Particle Interactions of Fluticasone Propionate and Salmeterol Xinafoate in Advair Diskus®

Martin Jetzer^1,2, Bradley Morrical¹, David Fergenson³ & Georgios Imanidis²

¹Novartis Pharma AG, Global Development, Novartis Campus, Lichtstrasse 35, Basel, 4056, Switzerland

²University of Basel, Department of Pharmaceutical Sciences, Klingelbergstrasse 50, Basel, 4056, Switzerland

³Livermore Instruments Inc., 2038 Livingston Street, Oakland CA, 94606, USA

Summary

Particle co-associations between the active pharmaceutical ingredients (APIs) fluticasone propionate (FP) and salmeterol xinafoate (SX) were examined in a dry powder inhaled (DPI) combination product. Single Particle Aerosol Mass Spectrometry (SPAMS) was used to investigate the particle interactions in Advair Diskus® (500 mcg FP/50 mcg SX). A simple rules tree was used to identify each compound, either as a single API or co-associated at the level of the individual particle, using unique marker peaks in the mass spectra for the identification of each drug. High levels of API co-association were observed in the aerosols emitted from Advair Diskus®. The majority of the detected SX particles were found to be in co-association with FP in the tested device. Another significant finding was that rather coarse FP particles and fine SX particles were forming the particle co-associations in the DPI product.