| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2483949 | Journal of Drug Delivery Science and Technology | 2007 | 7 Pages |
In dry powder formulations for inhalation, the micronized active substance is usually diluted with a mixture of coarse and fine carrier particles in order to increase its flowability and dispersion properties. Considering a selected DPI fluticasone propionate (Flp)-coarse (CL) and fine (FL) lactoses ([Pharmatose DCL 21/Microfine 80/20] 1:499 w/w) composition in terms of drug deposition, the aim of the present study was to establish the optimal blending conditions in three types of mixing equipment, and to determine the effects of FL on the mixing homogeneity and dispersibility of Flp. The Flp-lactose ternary mixtures were prepared by first premixing the two lactoses (CL/FL) in five different ratios: 100/0; 99/1; 90/10; 80/20; 0/100 (w/w). Then Flp was added and the blending was carried out at three rotational speeds (low, medium and high) in a three-dimensional motion mixer (Turbula 2C), a planetary mixer (Collette MP-20) and a high-shear (Mi-Pro) mixer. The incorporation of a large proportion of FL (20%) considerably improved the aerosol performance (FPD = 87 μg) but greatly reduced the content uniformity of Flp when the blending was performed in the Turbula mixer (relative standard deviation, RSD > 20% after 20 min irrespective of the selected speed). The achievement of a homogeneous mixture (RSD < 3%) required the use of powerful shear mixers (Colette MP-20 or Mi-Pro) operating at moderated rotational speeds to avoid the phenomenon of powder segregation and dust generation.
