Paulo Serra1, Jared Hall1, Irene Rossi1, Jagdeep Shur1 & Robert Price1
1Nanopharm Ltd, An Aptar Pharma Company, Cavendish House Hazell Drive, Newport NP10 8FY, United Kingdom
Summary
Particle size distribution (PSD) is possibly one of the most important critical material attributes (CMAs) in bioequivalence studies for nasal spray. The use of automated imaging, combined with Raman spectroscopy (MDRS), allows to measure the PSD of each component present in the formulation individually. The aim of this study was to highlight the importance of morphological filters application for MDRS method development and how they can be efficiently selected though a screening Design of Experiment (DoE). Twenty two different filters combinations have been used to analyse Flonase® formulation (fluticasone propionate, FP and microcrystalline cellulose – MCC). Only one single combination (number 10) showed a good power of particle selection, proven also by Raman identification: only 6 particles of microcrystalline cellulose been picked as potential FP particles between the one screened by the filters applied. Results obtained showed that and approach by a screening DoE can lead to a quickly defined working set of filters for the measurement of just API particles in nasal spray. A further DoE for optimization of these parameters will increase the method efficiency of particle detection. Moreover, the same approach will be applied to nasal formulations comprising suspended proteins and peptides in order to show the importance of filters and automated imaging combined with Raman for PSD and morphological analysis of such complex products.
Key Message
Application of morphological filters in automated imaging allows to more efficient and time-cost effective development of a suitable method for characterization of complex nasal spray suspensions in bioequivalence study. Particularly, a screening DoE was useful to select the most relevant filters for identification and PSD determination of API in Flonase® formulation.