Applying QbD principles in early DPI development: designing for robustness through Design Space exploration

João V. Fernandes, Isabel S. Lopes, Filipe Neves

A major benefit of performing Design Space exploration as early as possible during Dry Powder Inhaler (DPI) development is the identification of optimal design parameters as well as the quantification of the robustness of such optimal design points. Design Space exploration is a cornerstone of Quality by Design (QbD) based approaches to pharmaceutical product development and its application to inhalation device development has been proposed.
Within the context of the development of an enhanced version of the currently marketed TwinCaps® DPI with an enlarged powder cavity targeting effective high dosage drug delivery to the lungs, the current work reports an exploration of the Design Space considering the interactions of device, particle engineering and formulation design variables on key inhalation drug product performance attributes, such as Emitted Mass (EM) and Fine Particle Fraction (FPF5μm/EM). For that purpose, an experimental characterization of the Design Space defined by the i) device powder cavity outlet blockage σ, defined as the ratio between obstruction and total channel area (design parameter), ii) model drug particle size and iii) formulation fill weight, was performed using rapid prototyping technologies together with fast screening analytical methods.
Results from the current Design Space exploration revealed that the selection of a device powder outlet blockage between 0.7 and 0.85 delivers a robust EM and FPF5μm/EM performance across the interval of particle size and formulation fill weight values evaluated

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