Carlotta Giulieri1, Gianluca Trentin2, Stefano Cagliero2 & Aurelie Schoubben1
1University of Perugia, via del Liceo 1, Perugia (PG), 06123, Italy
2Aptuit an Evotec company, via Alessandro Fleming 4, Verona (VR), 37135, Italy
Summary
Aim of the current work was to optimize process and composition of previously studied Dry Powder for Inhalation (DPI) using anti-tussive Levo-Dropropizine as Active Pharmaceutical Ingredient (API). The previous work based on Design of Experiments (DoE), was performed to select a carrier-based formulation of Levo-Dropropizine, studying different grade of Lactose, different concentration of Magnesium Stearate, Drug Load (DL) and blending procedure. However, micronized Levo-Dropropizine with selected formulation didn’t give satisfactory inhalation performance. During the present work co-micronization with Magnesium Stearate and replacement of fine carrier with micronized Curcumin demonstrate to improve API inhalation performance. Surprisingly, less agglomeration between particles by co-micronization technique, shape similarity of micronized Curcumin with fine Lactose and usage of it as carrier into the formulation, improve aerosolization of Levo-dropropizine. Several formulations were produced, studying different combination and composition to better understand the impact of each component. Micronized and co-micronized APIs were characterized by High Performance Liquid Chromatography (HPLC), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Laser Light Scattering (LLS). Blends and capsules were manufactured and characterized by Blend Homogeneity (BH), FT4 Rheometer, Next Generation Impactor (NGI) and Dosage Unit Sampling Apparatus (DUSA). Promising results were obtained with reduced agglomeration behaviour followed by increase of ED, FPF and FPD with reduced retention of material inside capsules, device and mouthpiece.
Key Message
Co-micronization process of Levo-Dropropizine and Magnesium Stearate reduced the micronized API agglomeration. Furthermore, thanks to shape similarity between micronized Curcumin and fine Lactose Monohydrate, Curcumin was used as carrier in DPI formulation of Levo-Dropropizine. The combination of these two approaches, permitted a deeper increase of inhalable particles of Levo-Dropropizine.