The pharmaceutical respiratory inhalation sector is entering its second major propellant transition. In response to the Montreal Protocol requirements, the first transition moved pressurized metered dose inhalers (pMDIs) away from ozone-depleting chlorofluorocarbons (CFCs such as CFC-11) to hydrofluoroalkanes (HFAs), principally HFA-134a and HFA-227ea. These HFAs eliminated the ozone-depletion concern but unfortunately retained high global warming potential (GWP).

Climate change regulation is now driving a further transition. Following the Montreal Protocol, the Kyoto Protocol and the related Kigali Amendment established a global hydrofluorocarbon phasedown trajectory. For pMDIs, the challenge is to decarbonize without compromising patient access, inhaler performance or therapeutic continuity.

Solstice Advanced Materials is addressing this challenge by supplying customers with commercially available low GWP, non-ozone depleting and non-flammable propellant used to create next-generation respiratory care solutions.

Carrier-based interactive powder mixtures are a cornerstone of drug delivery by inhalation, yet optimization is hampered by the complex interplay of various carrier particle properties including their geometry. Conventional approaches for carrier particle manufacture such as milling, sieving or spray drying can modify multiple attributes simultaneously, making it challenging to assess the effect of particle geometry. To address this, two innovative strategies were applied and are presented in this article: in-silico modeling and the use of 3D-printed carrier particles.

Four particle geometries—Sphere, Soccerball, Rollingknot and Pharmacone—were investigated, with the Pharmacone exhibiting superior performance. Next, a parametric Satellite geometry was created and optimized through a fully automated in-silico workflow integrating Bayesian optimization, identifying design rules for spike dimensions and surface features. These studies demonstrate that carrier geometry is a critical determinant of drug detachment and aerosolization efficiency. Together, advanced 3D printing and in-silico optimization can provide a powerful framework for designing carrier particles with tailored geometries, offering new opportunities to enhance the performance of dry powder inhalers.

June 2026 marked the 25th anniversary of the shipment of the first Next Generation Impactor—the NGI™. In the late 1990s, the NGI Consortium of pharmaceutical companies defined the need for and the performance requirements for the NGI and awarded a contract to MSP Corporation to devise a suitable impactor. With substantial input from Consortium members, the NGI was then designed, patented and manufactured by MSP Corporation. The NGI has since become the preferred multi-stage impactor across the inhalation community.

In an interview, Daryl Roberts and Jolyon Mitchell reflect on manufacturing considerations encountered during the early commercialization of the NGI. In addition, two previously published articles by Roberts and Mitchell discuss the rationale and outcomes of manufacturing controls for the NGI. The first article describes improvements in control of the stage nozzle diameters, the most important feature affecting the aerodynamic size-fractionating performance. The second article discusses control of the more subtle, but often equally important, collection surface profile presented to the incoming aerosol particle.