Towards a standardised dissolution methodology for orally inhaled drug products

Karin Somby^1,2, Ivana Tomic², Martin Hingle² & Ben Forbes¹

¹King’s College London, Stamford Street, London, SE1 9HN, UK

²Novartis Pharma AG, Fabrikstrasse 2, Novartis Campus, Basel, 4056, Switzerland

Summary

The role of dissolution in pulmonary drug delivery has received significant interest over the last decade, with intensifying research into dissolution methods for orally inhaled drug products (OIDPs). Proposers of an inhaled biopharmaceutical classification system (iBCS) argue for dissolution as a quality attribute of inhaled aerosol medicines that contain drugs with low aqueous solubility. OIDPs containing the corticosteroid fluticasone propionate (FP), e.g., Advair Diskus, fall into the category of products for which dissolution may play a significant role in product performance. The aim of this study was to take advantage of the learnings in the scientific literature and configure an in vitro aerosol deposition and dissolution system for inhaled dosage forms that is: (i) predictive of in vivo performance, and (ii) amenable to standardisation. Respirable fractions of Advair Diskus were collected using a Next Generation Impactor (NGI) and transferred to a Transwell^® chamber in which dissolution conditions were selected based on simplicity, previously published literature and bio relevance. First, a Transwell^® dissolution system was established with a dissolution medium containing phosphate buffer and 0.15% surfactant (SDS) which was benchmarked to the published solubility of FP in more representative epithelial lung lining fluids. The dissolution of different dosage strengths (100 µg, 250 µg, and 500 µg FP in Advair Diskus) were evaluated and found to differ with previously reported data potentially due to the aerosol collection and use of sink and non-sink conditions. This work contributes to the development of systems with the potential to become standardised dissolution procedures for OIDPs.

Key Message

In response to recent frameworks emphasising the importance of dissolution for certain classes of inhaled medicines, we have taken learnings from the literature to configure a dissolution method that combines simplicity and bio-relevance. This contributes to the iterative development of systems with the potential to become standardised dissolution procedures for OIDPs.