De-agglomeration Effect of the US Pharmacopeia and Alberta Throats on Carrier-Based Powders in Commercial Inhalation Products

• Published in: The AAPS journal Vol. 17; no. 6; pp. 1407 - 1416
• Main Authors: Leung, Sharon Shui Yee, Tang, Patricia, Zhou, Qi (Tony), Tong, Zhenbo, Leung, Cassandra, Decharaksa, Janwit, Yang, Runyu, Chan, Hak-Kim
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2015
• Subjects: Administration, Inhalation; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - metabolism; Dry Powder Inhalers - methods; Humans; Lung - drug effects; Lung - metabolism; Particle Size; Pharmacology/Toxicology; Pharmacopoeias as Topic; Pharmacy; Pharynx - drug effects; Pharynx - metabolism; Research Article; United States; United States; USP throat; dry powder inhaler; idealized mouth-throat geometry; lactose carrier; powder aerosols
• ISSN: 1550-7416; 1550-7416
• DOI: 10.1208/s12248-015-9802-0

The US pharmacopeia (USP) and Alberta throats were recently reported to cause further de-agglomeration of carrier-free powders emitted from some dry powder inhalers (DPIs). This study assessed if they have similar influences on commercially available carrier-based DPIs. A straight tube, a USP throat, and an Alberta throat (non-coated and coated) were used for cascade impaction testing. Aerosol fine particle fraction (FPF ≤ 5 μm) was computed to evaluate throat-induced de-agglomeration. Computational fluid dynamics are employed to simulate airflow patterns and particle trajectories inside the USP and Alberta throats. For all tested products, no significant differences in the in vitro aerosol performance were observed between the USP throat and the straight tube. Using fine lactose carriers (<10 μm), Symbicort ® and Oxis ™ showed minimal impaction inside the Alberta throat and resulted in similar FPF among all induction ports. For products using coarse lactose carriers (>10 μm), impaction frequency and energy inside the Alberta throat were significant. Further de-agglomeration was noted inside the non-coated Alberta throat for Seretide ® and Spiriva ® , but agglomerates emitted from Relenza ® , Ventolin ® , and Foradil ® did not further break up into smaller fractions. The coated Alberta throat considerably reduced the FPF values of these products due to the high throat retention, but they generally agreed better with the in vivo data. In conclusion, depending on the powder formulation (including carrier particle size), the inhaler, and the induction port, further de-agglomeration could happen ex-inhaler and create differences in the in vitro measurements.