The research paper investigates the influence of primary crystallization conditions on the mechanical properties and the secondary processing behavior of Fluticasone Propionate for carrier-based dry powder inhaler (DPI) formulations. The study uses a nanoindentation approach to measure the mechanical properties of primary crystals of Fluticasone Propionate crystallized using different anti-solvents.
The variations in the mechanical properties, as highlighted by the range of Young’s modulus measured for different crystallization conditions of Fluticasone Propionate, were shown to directly influence the particle size reduction efficiencies upon micronization. A low Young’s modulus crystal of Fluticasone Propionate required multiple milling cycles to sufficiently reduce the particle size distribution to a respirable size range.
These variations in mechanical properties and differing energy requirements for particle size reduction were also shown to influence the cohesive-adhesive properties of the Fluticasone Propionate samples with respect to lactose monohydrate and in combination with Salmeterol Xinafoate. These changes in the interfacial chemistry of the secondary processed Fluticasone Propionate may ultimately lead to variability in formulation performance of the DPI formulations, as suggested by the aerosolization performance of these samples when formulated in combination with Salmeterol Xinafoate.
By gaining an understanding of how the primary crystallization process affects secondary processing, interfacial forces, and the functionality of a DPI formulation, greater quality control in the formation of these complex products may be achieved.
