Early Development Tools for Respiratory Drug Products
Spray pattern and plume geometry have long been established as required tests for orally inhaled and nasal drug product (OINDP) characterization. These tests are important indicators of aerosolization, spray performance and subsequent bioavailability (BA) of the delivered drug. The industry guidelines for metered dose inhalers from the United States Food and Drug Administration (US FDA) state that, “Various factors can affect the spray pattern and plume geometry, including the size and shape of the actuator orifice, the design of the actuator, the size of the metering chamber, the size of the stem orifice of the valve, the vapor pressure in the container, and the nature of the formulation.” Understanding these effects becomes essential to successful drug development and approval.
Proveris’ SprayVIEW Measurement System is the most comprehensive platform evaluating all aspects of a product that will take you from early development through batch release testing in production. Because spray pattern and plume geometry measurements are so sensitive to subtle changes in device, formulation, and human usage parameters, it has become a very powerful tool and gold standard in the world of OINDP development. Proveris recommends getting spray pattern data as early on as possible in the development process in order to get a good benchmark for product performance before tweaking and optimizing device design or even formulation.
Our study, ‘Spray pattern: A rapid and sensitive early development tool for respiratory drug products’ was designed to examine spray pattern against changes in the sump design for pressurized metered dose inhaler (pMDI) products, specifically orifice diameter, orifice length and sump chamber depth parameters (Figure 1). These parameters were found, in a previous study, to have the most significant effects on spray performance. The results here corroborate the previous study’s findings and demonstrate how small variations in sump design, as well as variability introduced by other factors (canister, valve, formulation), drive significant changes in spray pattern area (Figure 2).
Sump design has a robust and reproducible effect on the nature of spray pattern, independent of formulation factors, as observed by the similar spray pattern area trend across sumps for ProAir and Ventolin. The effect of formulation factors is evident from differences in the spray pattern area values and variability between the two products. Multiple characteristics of spray pattern, such as ovality and time-based intensity measurements can reveal subtle performance defects and design limitations. These results show that a combination of formulation properties and actuator design can have an impact on spray pattern ovality, whether it be direct or indirect. This study has been a small example of the value that spray pattern can have as a tool, and a means for providing rapid results early in reference or generic product development. This type of analysis can be applied to other aspects of product development not examined in this study, such as valve, canister and mouthpiece design or formulation components, as well as to other types of devices including nasal spray products.