Application of micro-Raman Spectroscopy for Automatic Chemical Identification and Size Distribution Measurement of API Particles in Pharmaceutical Suspensions. The case of Fluticasone Propionate in Suspension Nasal Sprays.
Alexios Tsiligiannis1, Varvara Zoumpliou1, Argyro-Nektaria Taouktsi1, Michail Lykouras2, Ioanna Chrisikou 3, Christos Kontoyannis2,3 & Malvina Orkoula2
1Elpen Pharmaceuticals Co. Inc., 95, Marathonos avenue, Pikermi, 190 09, Greece
2Department of Pharmacy, University of Patras, University Campus, GR-26504 Rio Achaias, Greece,
3Institute of Chemical Engineering Sciences, Foundation of Research and Technology-Hellas (ICE-HT/FORTH),
GR-26504 Platani Achaias, Greece
The current regulatory framework allows for the in vitro comparison of inhalation and nasal products, under specific restrictions and requirements. One of the most challenging prerequisites is the comparison focusing on component identification and particle size determination, in an automated, unbiased and valid manner. In this study, a method for the automatic chemical identification of suspensions’ constituents and simultaneous determination of their particle size distributions (PSD) has been proposed. A micro-Raman spectrometer equipped with the ParticleFinderTM software was used to identify the suspended active pharmaceutical ingredient (API) and excipients particles in azelastine hydrochloride/fluticasone propionate nasal spray suspensions and to assess their size distribution. A “generic” nasal spray suspension has been developed as a therapeutic equivalent alternative to Dymista® nasal spray. Two batches of reference product differing in their shelf life and one batch of test product were tested and compared. No individual azelastine HCl particles were detected possibly due to API dissolution and potential precipitation as an extremely fine particle size distribution. Fluticasone propionate API and Avicel® CL-611 excipient were clearly identified and their particle size distribution was assessed. The method was successful in identifying the intended attributes, as well as potential aging effects: in several expired formulations Fluticasone propionate particles exhibited aggregation tendency captured by the proposed technique.
Micro-Raman spectrometer and ParticleFinderTM software were employed successfully in order to chemically identify the solid particles of nasal spray samples and simultaneously measure their size distribution.