Comparison of HPMC Inhalation-Grade Capsules and Their Effect on Aerosol Performance Using Budesonide and Rifampicin DPI Formulations

Abstract

Despite the fact that capsules play an important role in many dry powder inhalation (DPI) systems, few studies have been conducted to investigate the capsules’ interactions with respirable powders. The effect of four commercially available hydroxypropyl methylcellulose (HPMC)inhalation-grade capsule types on the aerosol performance of two model DPI formulations (lactose carrier and a carrier-free formulation) at two different pressure drops was investigated in this study. There were no statistically significant differences in performance between capsules by using the carrier-based formulation. However, there were some differences between the capsules used for the carrier-free rifampicin formulation. At 2-kPa pressure drop conditions, Embocaps® VG capsules had a higher mean emitted fraction (EF) (89.86%) and a lower mean mass median aerodynamic diameter (MMAD) (4.19 µm) than Vcaps® (Capsugel) (85.54%, 5.10 µm) and Quali-V® I (Qualicaps) (85.01%, 5.09 µm), but no significant performance differences between Embocaps® and ACGcaps™ HI. Moreover, Embocaps® VG capsules exhibited a higher mean respirable fraction (RF)/fine particle fraction (FPF) with a 3-µm–sized cutoff (RF/FPF < 3 µm ) (33.05%/35.36%) against Quali-V® I (28.16%/31.75%) ( P < 0.05), and a higher RF/FPF with a 5-µm–sized cutoff (RF/FPF < 5 µm ) (49.15%/52.57%) versus ACGcaps™ HI (38.88%/41.99%) ( P < 0.01) at 4-kPa pressure drop condition. Aerosol performance variability, pierced-flap detachment, as well as capsule hardness and stiffness, may all influence capsule type selection in a carrier-based formulation. The capsule type influenced EF, RF, FPF, and MMAD in the carrier-free formulation.

Inhalation Dosage Forms: A Focus on Dry Powder Inhalers and Their Advancements

“…The hardness of the capsules seemed to impact the degree of flap detachment and subsequent aerosol performance. This study emphasizes the importance of carefully selecting suitable capsules and highlights the importance of the relationship between capsule properties and formulation differences, advocating for further investigation of different capsule types to optimize the performance of novel inhaled formulations [182].…”

Emerging Process Modeling Capabilities for Dry Powder Operations for Inhaled Formulations

“…To deliver the product with an inhalation device, dry powder must be metered into a primary dose carrier like a capsule, blister, or reservoir . Given the fact that the capsule dose metering method is used by over 50% of all DPIs on the market, capsule filling instruments will be the focus here . A capsule is normally manually filled on a laboratory scale.…”

“…93 Given the fact that the capsule dose metering method is used by over 50% of all DPIs on the market, capsule filling instruments will be the focus here. 94 A capsule is normally manually filled on a laboratory scale. Due to the low fill weights of each dose, specialized dosing equipment is required for clinical and commercial uses.…”