Zhenbo Tong

Multi-scale modelling of powder dispersion in a carrier-based inhalation system.

ABSTRACTPurposeCarrier-based dry powder inhalers (DPIs) are widely used for rapid and convenient delivery of drug to the site of action. This work aimed to predict powder aerosolisation in DPIs through numerical modelling.MethodsA multi-scale modelling technique based on the combined computational fluid dynamics (CFD) and discrete element method (DEM) approach was developed.ResultsThe simulation results of the detachments of the drug particles from single carrier under different impact velocities and angles were comparable with those measured in the experiments in terms of fine particle fraction FPFloaded. Empirical equations were developed to link the detachment performance with impact velocity and impact angle. Then the dynamics of the carrier particles in Aerolizer® was simulated. The results indicated that the carrier-wall impaction was the dominant mechanism for drug aerosolisation performance. By linking the empirical equations with the carrier-wall impact energy, the predictions showed that for a given formulation mass with a fixed carrier/drug ratio, the inhaler performance decreased with carrier size and increased with air flow rate. Device empty efficiency, however, was independent with carrier size and flow rate.ConclusionsThe multi-scale model was able to provide quantitative information to better understand the aerosolisation mechanisms of carrier-based formulation.

Impact angles as an alternative way to improve aerosolisation of powders for inhalation

This study aims to investigate the role of impact angles on the de-agglomeration performance of powders for inhalation. Agglomerates of a model drug mannitol were impacted at customized impaction throats containing two angles (15-75 degrees and 45-45 degrees) or a single angle (15 degrees, 45 degrees and 90 degrees) using various air flow rates. The mass fraction of fine particles <5microm in the aerosol (FPF(Loaded)) was measured by a liquid impinger coupled to a laser diffractometer. Results showed that for the two-angle throats, there existed an optimal angle (45 degrees) and air flow (120lmin(-1)) for the FPF(Loaded), resulting from a balance between improved de-agglomeration and enhanced throat deposition with increasing air flow. When the throat contained two equal angles of 45 degrees , most powder deposition occurred at the first angle, indicating that the first angle was likely to cause major de-agglomeration, while the second angle might act as a facilitator for further break-up, but the deposition was minimum as the fragment sizes and velocity at the second impaction were smaller. This hypothesis was supported by further studies using single-angle throats and numerical simulation (DEM-CFD). These findings imply the potential importance of using angular design features for multiple impactions to improve DPI performance.

Does the United States Pharmacopeia Throat Introduce De-agglomeration of Carrier-Free Powder from Inhalers?

PurposeWe hypothesize that the USP induction port may de-agglomerate carrier-free powder emitting from dry powder inhalers (DPIs).MethodsAerosols emitting from a range of DPIs (Spinhaler®, Turbuhaler® and OsmohalerTM) and induction ports (USP throat, straight tube, Alberta idealized mouth-throat geometry (AG)) were sized by laser diffraction. Total drug recovery was obtained by HPLC and fine particle fraction computed. Air flow patterns were simulated using Computational Fluid Dynamics (CFD).ResultsThe straight tube did not de-agglomerate emitted powder. However, the USP throat and AG further de-agglomerated powders from the Spinhaler, but not the Turbuhaler and Osmohaler. While budesonide powder deposited similarly in all induction ports, deposition was significantly higher in the AG for both DSCG and mannitol. CFD revealed agglomerates impacting on the USP throat with higher localized velocity compared with the straight tube. CFD further showed a more complex flow pattern with high-velocity air jets in the AG, which explains the higher FPF for DSCG and the lower FPF for mannitol using the AG.ConclusionThe USP throat further de-agglomerated the emitted powder from the DPI when it did not sufficiently disperse the powder. Other tools such as laser diffraction may be used for cross-examining to avoid artifacts in the results.

Discrete Modelling of Powder Dispersion in Dry Powder Inhalers - A Brief Review.

The performance of a dry powder inhaler (DPI) depends on powder properties as well as the air and particle flows in the device. The main principle of powder dispersion is to overcome the inter-particle cohesion using various dispersion/ de-agglomeration forces. While different dispersion mechanisms have been identified, their relative importance under different conditions is less clear. The lack of understanding of these mechanisms is a major obstacle to the advance of pharmaceutical powder aerosol technology. This paper briefly reviews our recent effort in developing a combined computational fluid dynamics (CFD) and discrete element method (DEM) approach to gain such pivotal information. Dispersions under various specifically designed conditions were simulated to exam the role of individual dispersion mechanism. The air and particle flows were analysed at the particle scale and linked to dispersion performance characterised by fine particle fraction (FPF). In addition, the dispersion mechanisms of both drug only and carrier based formulations in a commercial inhaler were studied. Our work shows that the approach has the potential to develop a theoretical framework for designing new DPIs.

CFD analysis of the aerosolization of carrier-based dry powder inhaler formulations

This study applied computational fluid dynamics (CFD) analysis to investigate the role of device design on the aerosolization of a carrier-based dry powder inhaler (DPI). The inhaler device was modified by reducing the inlet size, decreasing the mouthpiece length and increasing the mesh grid voidage. The flow patterns in the inhaler device were examined. It was observed that there was no significant influence on the aerosol performance with the reduced mouthpiece. When the inlet size was reduced to one third of the original one, the fine particle fraction (FPF), defined as mount of inhalable fine particles below 5μm in the aerosol, was improved significantly from 17.7% to 24.3%. The CFD analysis indicated that the increase in FPF was due to increasing air velocity for the smaller inlet. No significant difference was shown in FPF when the grid voidage was increased, but more drugs deposited in the mouthpiece and throat.

CFD-DEM study the effect of carrier-drug mass ratio on the aerosolisation process in original and modified dry powder inhalers

Previous studies have reported that carrier-drug mass ratio has a significant influence on the aerosol performance of dry powder inhalation systems. This paper investigated the effect of carrier-drug mass ratio in different inhaler designs based on a multi-scale modelling technique combined computational fluid dynamics (CFD) and discrete element method (DEM) approach, aiming to develop better understanding of the aerosolisation mechanism of carrier-based formulation . Different formulations containing drug (salbutamol sulphate) and carrier (lactose) were used in experimental and numerical works with varied carrier-drug mass ratios ranging from 1:10 to 1:200. The fine particle fractions (FPFs) in the original and cross grid inhaler-throat model were measured to characterize the aerosolisation performance. The dynamics of the carrier particles in the original and cross grid inhaler-throat model were simulated. The experimental results showed that the significant difference between the original and cross-grid design for the pure drug but not for the carrier system. The numerical results showed that there was no much different in FPFs until a critical threshold was exceeded when the drug loading increased.