Effect of Device Design on the Aerosolization of a Carrier-Based Dry Powder Inhaler—a Case Study on Aerolizer® Foradile®

Abstract

Abstract. The objective of this study is to investigate the effect of device design of the Aerolizer ® on the aerosolization of a carrier-based dry powder inhaler formulation (Foradile ® ). The Aerolizer was modified by reducing the air inlet size and mouthpiece length to 1/3 of the original dimensions, or by increasing the grid voidage. Aerosolization of the powder formulation was assessed on a multi-stage liquid impinger at air flow rates of 30, 60, and 100 L/min. Coupled CFD-DEM simulations were performed to investigate the air flow pattern and particle impaction. There was no significant difference in the aerosolization behavior between the original and 1/3 mouthpiece length devices. Significant increases in FPF total and FPF emitted were demonstrated when the inlet size was reduced, and the results were explained by the increases in air velocity and turbulence from the CFD analysis. No significant differences were shown in FPF total and FPF emitted when the grid voidage was increased, but more drugs were found to deposit in induction port and to a lesser extent, the mouthpiece. This was supported by the CFD-DEM analysis which showed the particle-device collisions mainly occurred in the inhaler chamber, and the cross-grid design increased the particle-device collisions on both mouthpiece and induction port. The air inlet size and grid structure of the Aerolizer ® were found to impact significantly on the aerosolization of the carrier-based powder.KEY WORDS: aerosolization; computational fluid dynamics; device design; discrete element method; dry powder inhalers.

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

“…Secondly, Foradil ® Aerolizer ® showed comparable FPF among the three noncoated induction ports. Zhou et al (14) reported that the detachment of drug particles from the lactose carrier surface was mainly achieved inside the inhaler prior to entering the throat. Further de-agglomeration was, therefore, not expected to take place inside the Alberta throat.…”

“…The relative contributions of the deagglomeration mechanisms for specific inhalation products are dependent upon the inhaler design and powder formulation (11)(12)(13)(14). Further de-agglomeration could, therefore, happen ex-inhaler in two ways: (i) artificial deagglomeration as particles bounce/re-entrain from the surface of an in vitro throat and (ii) de-agglomeration caused by the transient flow acceleration at the restricted region inside the Alberta throat which could occur in vivo as powder passing the mouth-throat area.…”

“…While carrier-free powder agglomerates break up into smaller fragments and/or primary drug particles, drug particles in carrier-based systems have to detach from the carrier surfaces via sliding and/or rolling (14). Due to the intrinsic difference in the dispersion mechanisms, predicting the effect of throat-induced de-agglomeration for carrier-based systems on the basis of the carrier-free counterparts may not be valid.…”

Dry powder inhalers in COPD, lung inflammation and pulmonary infections

“…This emphasizes the need for the physician to know about the patient's inspiratory capacity and device performance capacity in prescribing DPI. There has been inter-and intrapatient variability in peak inhalation flow rate measurements making this selection difficult [76]. Nevertheless, the ultimate relationship between the physicochemical characteristics of the powder and the inhaler design will decide the aerosolization, de-aggregation and dispersion characteristics of the drug particles.…”

Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery

“…Although several in vitro apparatus such as twin-stage impinger (Haghi, Traini, & Young, 2014), multistage liquid impinger (Zhou et al, 2013) and cascade impactors (M. Chen, Romay, Li, Naqwi, & Marple, 2016) have been used to evaluate the particle deposition according to the size of particles, these methods could not totally imitate structures of upper and lower respiratory tracts. Rodent models such as rats and guinea pigs are usually employed for pulmonary dosing; however, mice are a greater technical challenge in lung dosimetry and collection of multiple blood samples due to smaller body size and limited volume of body blood.…”