Summary

A DoE study was conducted to analyse the effect of actuator geometry on the aerodynamic particle size distribution (APSD) profile of a generic solution pMDI. The relationship between actuator geometry and key aerodynamic particle size metrics were determined; the study provided a more complete understanding of how the actuator influences the APSD. The data showed that aerodynamic performance can be modified by making changes to the geometry of the actuator. Characteristics such as fine particle mass, throat deposition, mass median aerodynamic diameter and dose emitted from the actuator were studied and found to be significantly influenced by geometric alterations. To increase fine particle mass, orifice diameter can be decreased (and vice-versa). Correspondingly, throat deposition is decreased when orifice diameter is decreased (and vice-versa). Orifice diameter was highlighted as a statistically significant contributor to the variance in the response (p=7.83×10^-7, p=6.7×10^-10). To increase emitted dose, jet length can be increased (and vice-versa). The jet length was highlighted as a statistically significant factor in influencing actuator deposition, inferred by ex. actuator recovery, and MMAD (p=1.04×10^-5, p=0.005). The relationships which have been developed aid in the development of the product and increase the chance of regulatory acceptance of an in-vitro only submission. The APSD profiles of the test product, using each actuator variation, was compared to the reference product to determine the closest match thereby facilitating an in-vitro data based submission of a generic solution pMDI.  

Key Message

The statistically designed study highlighted the actuator geometry combinations which provided an APSD profile which closely matched the reference product. The key relationships, derived from the analysis of a full-factorial design, aid in the development of a generic solution pMDI and regulatory acceptance of an in-vitro only submission.