The effect of lactose fines, magnesium stearate, choice of mixer and mixing process on the performance of adhesive mixtures for inhalation

Sammanfattning: Dry powder inhaler (DPI) formulation is a major area of interest since they are employed by the healthcare system to treat relevant chronic diseases like asthma. Previous research has established that the manufacturing process and formulation composition are key for the active pharmaceutical ingredient to reach the lungs and achieve therapeutic effects. The aim of this study was to research the effect of lactose fines and magnesium stearate as well as mixing processes on the performance of adhesive mixtures for inhalation. The following research work was conducted by employing two mixers: Low shear (Turbula®) and high shear (Diosna®) for the manufacturing of the formulations. Three formulations were prepared varying the amount of excipients and mixing time, 27 batches were produced and filled into Novolizer® devices. Micronized budesonide was used as the active pharmaceutical ingredient. Quality control parameters like poured bulk density, drug content assay, and mixing homogeneity were executed. Formulation performance was analyzed by doing particle-size distribution analyses done mostly in an Andersen Cascade Impactor, although Next Generation Impactor was also used. Fine Particle Fraction (FPF) and Fine Particle Dose (FPD) were the central parameters to judge formulation performance. It was found that both lactose fines and magnesium stearate can improve formulation performance. In addition, high shear mixer formulations presented higher FPF values than low shear formulations. These findings suggest that lactose fines and magnesium stearate are key ingredients for an improved formulation performance and that high shear mixing is preferred to enhance FPF for DPIs.