Analytical challenges and regulatory perspectives in the development of soft mist inhalers (SMIs)

This article provides an overview of parameters that should be investigated during early development and routine testing of a soft mist inhaler (SMI). For reliable results, the methods should be validated for the unique properties of the aerosol generated by the SMI. Moreover, a thorough understanding of the device as well as the formulation characteristics is necessary to identify the critical attributes contributing to the overall quality of the aerosol ex-device.

In general, an SMI is treated similarly to other products containing solutions for oral inhalation with regard to physicochemical properties such as assay, related substances, pH, osmolality, etc. Testing differs mainly in the assessment of pharmaceutical performance, i.e., the quality of the aerosol plume emitted ex-device. In addition to general physicochemical tests required for inhalers, an SMI requires tests specific to the unique feature of a slow-moving gentle mist of fine droplets and the device mechanisms required to achieve this. In particular, conventional spray pattern, plume geometry and plume velocity tests are not sufficient, as these tests were historically developed as quality control methods for evaluating pMDIs and nasal devices, which typically comprise injection-molded nozzles and corresponding potential defects.