四色AV

In this article, Rui Churro, PhD, Senior Scientist, Carolina Lopes, Associate Scientist, and Jo茫o Pires, PhD, R&D Manager, all of 四色AV鈥檚 Inhalation and Advanced Drug Delivery group, discuss the value of rheological characterisation of powders to expedite and de-risk the scale-up of DPI capsule-filling processes.

Composite particles are gaining traction as an alternative formulation strategy for dry powder inhalers. Typically, these engineered particles present low densities and small aerodynamic particle size, promoting an effective delivery to the lung. However, these unique properties can also raise operational challenges, such as poor flowability and powder agglomeration, during downstream filling processes. Since dry powder inhalers may contain doses as low as few milligrams, it is essential to understand the rheologic properties of the filled powders and select the best filling technology/conditions towards reaching the required filling accuracy.

四色AV has been deeply investing in developing formulation/process development strategies together with advanced characterization tools towards anticipating operational and performance risks from very early stages and, in this way, minimize development effort at both lab and manufacturing scales. In this article, different case-studies are presented to exemplify how such methodologies can support capsule filling process development of composite particles, with different formulations, technologies and manufacturing scales.

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Key learnings

• Composite formulations are a highly promising solution for dry powder inhalers but can create multiple challenges namely during the downstream capsule filling process, such as poor flowability and severe powder agglomeration;
• Through advanced rheologic characterization tools and a QbD-based process development it is possible to anticipate operational and performance risks from early stages and act upon them through formulation and process optimization;
• The presented case-studies indicate a clear dependence of the operational ranges on the rheological properties of the formulation and similar relation between the filling process parameters and process/product performance across scales;
• The shared process development approach allows 四色AV to accelerate the transfer of capsule filling processes to larger scales, for both clinical and commercial supply, by minimizing the required development effort and the level of risk associated with each scale-up.

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