Advancing the Quality by Design Paradigm to Accelerate Early Phase Development of Dry Powder Inhaler Formulations

Jagdeep Shur, Robert Price

We have developed a rapid early phase formulation development platform DPIs, which introduces a material science based approach to product development. Such an approach warrants the application of advanced analytical tools to characterise material properties at the mesoscale and provide analysis of formulation microstructure. Owing to the complexity of a carrier DPI formulation, it is critical to measure the CMAs of the input materials that relate the fluidization and de-aggregation of the powder dose from the device to drug product performance. A key CMA of the API component of DPI formulations, therefore, includes the determination of the cohesive-adhesive balance (CAB) of the drug particles with respect to the lactose carrier. In conjunction with investigation of the API CMAs, it is important to correlate the relationship with CPPs of unit operations such as blending. The role of blending process is to achieves a chemical attribute (e.g. good blend homogeneity) and also enables manipulation of a physical attribute (e.g. fine particle mass). This allows the formation of a design space for the formulation performance whilst taking into consideration the API CMAs. We have demonstrated that such an approach provides a pathway to expedite rapid early phase formulation development.

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