Summary

Despite the major role capsules have in many dry powder inhalation (DPI) systems, few studies have been performed to examine the interaction of the capsules with respirable powders. This study of four commercially available HPMC inhalation grade capsule types investigated their effect on aerosol performance of two model DPI formulations (lactose carrier and a carrier free formulation) at two different pressure drops. No statistically significant performance differences were found in carrier-based formulation. Using carrier-free rifampin formulation, Embocaps^® VG capsules exhibited higher mean emitted fraction (EF) (89.86%) and lower mean mass median aerodynamic diameter (MMAD) (4.19) than Vcaps® (Capsugel) (85.54%, 5.10) and Quali-V^® I (Qualicaps) (85.01, 5.09) at 2 kPa pressure drop conditions (p < 0.05), but no significant performance differences between ACGcaps™ HI and Embocaps^® VG in this study. At 4 kPa pressure drop condition, Embocaps^® VG demonstrated a higher mean respirable fraction (RF)/fine particle fraction (FPF) with a 5 µm size cut-off (RF/FPF < 5 µm) (49.15% / 52.57%) versus ACGcaps™ HI (38.88 / 41.99%) (p < 0.01), and a higher mean RF/FPF with a 3 µm size cut-off (RF/FPF < 3 µm) (33.05% / 35.36%) versus Quali-V^® I (28.16% / 31.75%) (p < 0.05). Therefore, optimal capsule type varies depending on the DPI formulation and the desired performance outcomes. For the carrier-based formulation, aerosol performance variability as well as the pierced-flap detachment may also drive selection of capsule type. For the carrier free formulation, capsule type influenced EF, RF, FPF, and MMAD.

Key Message

Capsule type selection for DPIs is a key decision to optimize product performance, avoid costly failures, depends on formulation type and desired outcomes. Additionally, there is a potential relationship between the flap created in the capsule during piercing and the aerosol performance of the inhaled powder.