Application of SmartTrack^® tools to the investigation of aerosolization and physico-chemical properties of vilanterol dry powder inhalers (DPIs)

Jared Hall¹, Elisavet Dimosthenous¹, Lucas Silva¹, Gonçalo Farias¹, David Gomez Lamarca ², Monica Capon Borrell², Robert Price¹, Jagdeep Shur¹ & Irene Rossi¹

¹Nanopharm, An Aptar Pharma Company, Grange Road, Cwmbran, NP44 3WY, United Kingdom

²Inke S. A., Carrer Argent 1, Barcelona, 08755, Spain

Summary

The influence of aerosolization and physico-chemical properties of vilanterol dry powder inhalers on the in vitro release rate (IVRR) was investigated, employing Nanopharm’s SmartTrack^®, a collection of tools, which can help in demonstrating bioequivalence. In a previous study, the discriminatory ability of in vitro release testing (IVRT) to highlight differences on particle size distribution of vilanterol batches was demonstrated. In this work, instead, we focused on understanding if the use of a different device and formulation composition could be distinguished by IVRT. A Relvar Ellipta^® (GlaxoSmithKline, UK) was dissembled and the content of the strips loaded in size 3 capsules and aerosolized with RS01 (Plastiape S.p.A., IT). Relvar Ellipta^® as it is was compared to an Ellipta device loaded with just a vilanterol strip, RS01 loaded with vilanterol formulation and the combination vilanterol/fluticasone furoate. Impactor sized mass (ISM) was collected with Nanopharm’s Dissohale and analysed by morphological directed Raman spectroscopy (MDRS) and IVRT. MDRS showed morphological equivalence between the four samples analysed, as expected. However, IVRR was significantly different between devices used. The capsule-based device delivered a faster release rate, showing a high initial release and a quicker plateau of the ISM compared to the Ellipta device. This outcome was inversely correlated to the circular equivalent mean diameter obtained by MDRS which was significantly lower for ISM delivered by RS01 compared to the Ellipta. The discriminatory ability of IVRT was demonstrated, particularly in assessing the influence of device employed for aerosolization on the IVRR and ISM particle size.

Key Message

SmartTrack^® is a collection of tools, which can be used to fast-track bioequivalence studies. Particularly, in vitro release testing was coupled with the orthogonal technique morphological directed Raman spectroscopy to discriminate the release rate of the impactor sized mass delivered by different inhalers and how it correlated to particle size.