Application of void forming index (VFI): Detection of the effect of physical properties of dry powder inhaler formulations on powder cohesion.

Dry powder inhaler (DPI) is an attractive alternative for non-invasive drug administration and can make the use of critical biopharmaceutical formulations more convenient for patients. Inhalation of biopharmaceutical formulations can provide targeted delivery to the lungs as well as systemic delivery. Generally, biopharmaceutical DPI formulations consist of highly cohesive powders that tend to agglomerate. For successful delivery to the lungs, the detection of powder cohesiveness and its effect on the performance of the formulations is mandatory. Herein, the effects of the physical properties of mannitol on the cohesiveness of DPI formulations were investigated. The powder cohesion was detected using the void forming index (VFI) measured by inverse gas chromatography (iGC) at 4 h (VFI), which was defined as the pressure drop ratio of 4 h purged sample to that of the initial sample. VFI was found to correlate well with the cohesiveness of DPI formulations. The amount of investigated samples required for VFI measurement was less than that required for conventional measurements. VFI showed a good relationship between the cohesiveness of DPI formulations and the physical properties of mannitol. Thus, VFI can be a reliable standard index to evaluate the cohesiveness of DPI formulations.