Karin Marek1, Anna Romanessi1, Judith Water1, Anna Vivani2, Andrea Silvestri2, Maribel Bógalo Huescar3, Ross Blezard3 & Irene Rossi1
1Harro Höfliger, Helmholtzstraße 4, Allmersbach im Tal, 71573, Germany
2Sterling, Via della Carboneria 30, Corciano, 06073, Perugia, Italy
3DFE Pharma, Klever Straße 187, Goch, 47568, Germany
Summary
Microstructural equivalence is required for local acting products that are qualitatively and quantitatively the same as the reference listed drug in terms of their active (API) and inactive pharmaceutical materials. In this study we have assessed the influence on the aerosolisation performance and in vitro dissolution of fluticasone furoate (FF) API batches engineered with a similar particle size distribution, but different morphology (prismatic-shape crystals vs needle-shape crystals). FF-lactose blends were prepared by high shear mixing, filled into blister strips and coiled into a dual blister strip device. Different drug morphology resulted in different specific surface area (SSA) which influenced the in vitro dissolution profile. Lower SSA determined a higher ISM and FPD for the prismatic-shape API but slowed down drug dissolution. The investigation of the FF agglomeration state in the ISM will additionally clarify the differences observed in the in vitro performance of formulations prepared with API with different morphology. Nevertheless, this study shows how understanding and controlling API’s physico-chemical properties and their effect on product performance is fundamental in DPI development. Further optimisation of FF morphology will be performed to expand the design space of the formulation, such that the in vitro performance can be fine-tuned based on bioequivalence requirements.