Influence of crystal form of ipratropium bromide on micronisation and aerosolisation behaviour in dry powder inhaler formulations

Shur, Jagdeep; Kubavat, Harshal A.; Ruecroft, Graham; Hipkiss, David; Price, Robert

doi:10.1111/j.2042-7158.2012.01522.x

Cited by 11 publications

(6 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Generally, DPI performance is determined by the design of the device ( e.g ., grid structure, mouthpiece length and geometry) 5–7 , the formulation and the patients’ respiration manoeuvre 4 ; a number of studies have recently been performed to investigate the dependency of DPI performance on these factors 8,9 . The influence of formulation properties on DPI performance, such as particle size 10 , particle concentration 11 , particle morphology 12 , particle surface roughness 13 , density and porosity 14 , crystal form 15 , electrostatic charge 16 , flowability 17 and the type of ternary additive, 18 has also been explored. The DEM or DEM–CFD approach was also applied to investigate the effects of impacts among particles/agglomerates/walls 19 , fluid flow 20 , particle adhesion 21 and device design 22 .…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional DEM–CFD analysis of air-flow-induced detachment of API particles from carrier particles in dry powder inhalers

Yang

Adams

2014

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

Air flow and particle–particle/wall impacts are considered as two primary dispersion mechanisms for dry powder inhalers (DPIs). Hence, an understanding of these mechanisms is critical for the development of DPIs. In this study, a coupled DEM–CFD (discrete element method–computational fluid dynamics) is employed to investigate the influence of air flow on the dispersion performance of the carrier-based DPI formulations. A carrier-based agglomerate is initially formed and then dispersed in a uniformed air flow. It is found that air flow can drag API particles away from the carrier and those in the downstream air flow regions are prone to be dispersed. Furthermore, the influence of the air velocity and work of adhesion are also examined. It is shown that the dispersion number (i.e., the number of API particles detached from the carrier) increases with increasing air velocity, and decreases with increasing the work of adhesion, indicating that the DPI performance is controlled by the balance of the removal and adhesive forces. It is also shown that the cumulative Weibull distribution function can be used to describe the DPI performance, which is governed by the ratio of the fluid drag force to the pull-off force.

show abstract

Section: Introductionmentioning

confidence: 99%

Three-dimensional DEM–CFD analysis of air-flow-induced detachment of API particles from carrier particles in dry powder inhalers

Yang

Adams

2014

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

show abstract

“…The desired particles size for aerosol delivery of drugs to the lungs requires a high-energy method to overcome the forces of attraction between molecules usually in the crystalline solid state to create a large surface area (Hickey A. and Ganderton D., 2001;Shur J. et al, 2012). The method, as depicted in Fig.…”

Section: Methods Of Manufacture and Particle Morphology 21 Millingmentioning

confidence: 99%

Complexity in Pharmaceutical Powders for Inhalation: A perspective

Hickey¹

2018

KONA

View full text Add to dashboard Cite

Pharmaceutical aerosol powders intended for inhalation are required to have unique performance characteristics that are highly dependent on their physico-chemical properties. A wide range of analytical methods have been applied to study particle structure, size distribution, surface properties and subsequent behaviour of powders with the intention of predicting their performance. However, particle interactions are dictated by complex fundamental forces that impact on the efficiency and reproducibility of delivery and thereby the quality, efficacy and safety of the final product. This manuscript reviews the interplay of physico-chemical properties of powder and the complex process and analytical variables that must be monitored and controlled to effectively predict powder performance.

show abstract

“…In addition, the adjustment of attachment between medicate particles and bond amongst bearer and medication particles was likewise found to influence the DPI performance [11,12]. To better comprehend the systems of the agglomeration and deagglomeration forms, numerous examinations have been directed to investigate the impacts of particle shape [13], particle size [14][15][16][17], particle concentration [18], particle surface roughness [19], density and porosity [20], surface energy [21], material properties [22], storage conditions [23], crystal form [24], electrostatic charge [25], flowability [26] and the type of ternary additives [27] on the performance of dry powder inhalers. Those customary and progressed test approaches gave a point by point comprehension of the overseeing factors in DPIs.…”

Section: Overviewmentioning

confidence: 99%

CFD DEM Analysis of a Dry Powder Inhaler

Badhan

Kotteda

Kumar

2019

Volume 2: Computational Fluid Dynamics

View full text Add to dashboard Cite

Dry powder inhalers (DPIs), used as a means for pulmonary drug delivery, typically contain a combination of active pharmaceutical ingredient (API) and significantly larger carrier particles. The micro-sized drug particles — which have a strong propensity to aggregate and poor aerosolization performance — mixed with significantly large carrier particles that are unable to penetrate the mouth-throat region to deagglomerate and entrain the smaller API particles in the inhaled airflow. The performance of a DPI, therefore, depends on entrainment the carrier-API combination particles and the time and thoroughness of the deagglomeration of the individual API particles from the carrier particles. Since DPI particle transport is significantly affected by particle-particle interactions, very different particles sizes and shapes, various forces including electrostatic and van der Waals forces, they present significant challenges to Computational Fluid Dynamics (CFD) modelers to model regional lung deposition from a DPI. In the current work, we present a novel high fidelity CFD discrete element modeling (CFD-DEM) and sensitivity analysis framework for predicting the transport of DPI carrier and API particles. The work integrates exascale capable CFD-DEM and sensitivity analysis capabilities by leveraging the Department of Energy (DOE) laboratories libraries: Multiphase Flow Interface Flow Exchange (MFiX) for CFD-DEM, and Trilinos for leading-edge portable/scalable linear algebra. We carried out a sensitivity analysis of various formulation properties and their effects on particle size distribution with Dakota, an open source software designed to exploit High-Performance Computing (HPC) capabilities of a massively parallel supercomputer. We developed wrappers to exchange information among these state-of-the-art tools for DPI.

show abstract

Influence of crystal form of ipratropium bromide on micronisation and aerosolisation behaviour in dry powder inhaler formulations

Abstract: Monohydrate and anhydrous crystals of IB exhibited similar mechanical properties and interfacial properties upon secondary processing. As a result, the performance of the DPI formulations were similar.

Cited by 11 publications

References 30 publications

Three-dimensional DEM–CFD analysis of air-flow-induced detachment of API particles from carrier particles in dry powder inhalers

Three-dimensional DEM–CFD analysis of air-flow-induced detachment of API particles from carrier particles in dry powder inhalers

Complexity in Pharmaceutical Powders for Inhalation: A perspective

CFD DEM Analysis of a Dry Powder Inhaler

Contact Info

Product

Resources

About