Jamie Clayton (Freeman Technology), Joana Pinto and Sarah Zellnitz (Research Center Pharmaceutical Engineering) discuss the benefits of multi-faceted powder characterisation in dry powder inhalation formulations and how it can support efforts to achieve net zero emissions.
Inhaled drug delivery technology has matured considerably in recent decades but there are now new issues to address. Efforts being made towards net zero emissions have highlighted the environmental impact of inhalers, notably metered dose inhalers (MDIs), while the Covid-19 pandemic has triggered the evaluation of inhaled therapies for both prevention and treatment. Addressing these new challenges calls for further evolution of inhaled drug delivery, which will simultaneously help with longer-standing goals, such as with the development of efficacious therapies for rarer infectious lung diseases and the better exploitation of the pulmonary route for systemic drug delivery.
With respect to environmental impact, there is much to recommend dry powder inhalers (DPIs). The hydro fluoroalkanes (HFAs) used as propellants in MDIs have a global warming potential 1430–3200 times that of CO2, which results in commercial MDIs having an estimated carbon footprint per actuation around ten times that of DPIs (based on full product lifecycle analysis). Switching to DPIs is an attractive strategy for companies working towards net zero. However, relying on a complex device to achieve acceptable drug delivery makes device recycling difficult. As such, developing simpler devices in combination with formulations engineered for optimal aerosolisation is a more sustainable option.
Covid-19 proceeds by rapid viral replication following infection via the respiratory tract, making the targeted, inhaled delivery of antiviral drugs potentially beneficial. While remdesivir has been successfully delivered intravenously, in hospitals, trials are underway to explore delivery by DPI or nebuliser, with DPIs being the easier option for routine, community-based use. Comparable trials are also in place for hydroxychloroquine (HCQ), as consensus grows that the lung airway concentration reached is too low to be effective when administered under a safe oral dosing regime. In place of twice-daily oral doses of 400 mg, the intended DPI dose is just 20 mg. Targeted delivery is expected to result in an efficacious concentration with this much lower dose, but 20 mg is still relatively high in inhaled drug terms.
The HCQ trials are being conducted using the Cyclops™ inhaler (Pure IMS, Roden, the Netherlands), a device with the efficiency to deliver high drug loads with minimal throat irritation. New devices, in combination with particle engineering, have extended the dosage range accessible with DPIs to >100 mg. This is an important trend, as increasing numbers of large molecules enter the respiratory drug pipeline, including proteins, oligonucleotides, antibodies and nanobodies, and for the treatment of infectious diseases, as exemplified by the use of high doses of tobramycin for the treatment of Pseudomonas aeruginosa infection in cystic fibrosis. Going forward, there is an expectation that formulators will need to deliver ever higher drug loads with powder formulations that are low density and exhibit poor flowability.
In this article, we show how multi-faceted powder characterisation can support effective DPI formulation within this changing landscape. Referencing studies led by researchers from the Research Center Pharmaceutical Engineering GmbH (Graz, Austria), we illustrate how measuring dynamic, shear and bulk powder properties delivers understanding that is inaccessible with traditional techniques to aid formulation optimisation.
Click here to read the article in OnDrugDelivery.