Table III.
Critical Quality Attributes of Inhalable Dry Powder Formulations and Their Characterization Methods and Requirements
| Quality attributes | Characterization techniques | Clinical impacts | Desired requirements |
|---|---|---|---|
| Geometric particle size distribution | Laser diffraction particle size analyzer | Particle deposition in airways | Optimization for MMAD in the range of 1 – 5 µm, maximized FPF and minimized GSD [11] |
| Small geometric particle size, low tapped density | |||
| (< 0.4 g/cm3 [102]) and large shape factor favors reduced particle DA [11] | |||
| Particle morphology (shape factor) | Scanning electron microscopy (SEM) | ||
| Particle tapped density | Volumeter; Graduated cylinder | ||
| Flowability | Carr index < 15; | ||
| Angle of repose < 35° | |||
| Electrostatic charge | Electrometer | Minimized (correlation with airflow rate should be established) [103] | |
| Drug loading | HPLC; LCMS/MS | Dose and dosing frequency | Normally maximized for flexible dose control |
| Drug assay and impurities | HPLC; UV; LCMS/MS | Product safety and efficacy | Compliance with pharmacopeia requirement |
| Residual solvent content | Thermogravimetric analysis (TGA) | Product quality and safety | Minimized; Compliance with pharmacopeia requirements |
| Crystallinity | Powder X-ray diffraction (PXRD) | Product quality | Determined based on drug release and stability requirements |
| Hygroscopicity | Dynamic vapor sorption (DVS) | Minimized | |
| Stability | Stability chamber | Fulfillment of ICH and local regulatory guidelines |