Inhalation Blend Microstructure: Identifying Metrics to Address Q3 Equivalence using Semi-automated X-Ray Microscopy

Assessing the microstructure of inhalation powder blends is important for assessment of Q3 microstructural equivalence, but it remains a challenge to examine a powder in its pre-actuated state. In this work, we demonstrate a robust, user-independent image analysis workflow for using X-ray Computed Tomography (XCT), allowing the fines-rich phase of different blend formulations to be visualized and quantified. The workflow provides qualitative and quantitative information on formulation microstructure. Qualitatively, differences in XCT-characterized microstructure were consistent with differences in aerosolization behavior of carrier lactose blends with micronized lactose, terbutaline sulfate and fluticasone propionate. Quantitatively, metrics for the local thickness of fines-rich phases were derived that quantify the thicker coating of fluticasone propionate fines around carrier lactose particles in a blend, compared to terbutaline sulfate or micronized lactose, which formed agglomerated regions of fines of lower density and a heterogeneous degree of association with carrier lactose particles. This approach links pre-actuated microstructure of inhalation powder blends with product performance and provides the first steps to the application of XCT to a range of dry powder inhalation products.