Quantifying Uncertainty in the Residence Time of the Drug and Carrier Particles in a Dry Powder Inhaler

2021 ◽  
Author(s):  
Antara Badhan ◽  
V M KRUSHNARAO Kotteda ◽  
Samia Afrin ◽  
Vinod Kumar
Keyword(s):  
Residence Time ◽  
Particle Density ◽  
Dry Powder Inhaler ◽  
Department Of Energy ◽  
Dry Powder ◽  
Throat Region ◽  
Particle In Cell ◽  
Pharmaceutical Ingredients ◽  
Fluidizing Agent ◽  
The Individual

Abstract Dry powder inhalers, used as a means for pulmonary drug delivery, typically contain a combination of active pharmaceutical ingredients (API) and significantly larger carrier particles. The micro-sized drug particles - which have a strong propensity to aggregate and poor aerosolization performance - are mixed with significantly large carrier particles that cannot penetrate the mouth-throat region to deagglomerate and entrain the smaller API particles in the inhaled airflow. Therefore, a DPI's performance depends on the carrier-API combination particles' entrainment and the time and thoroughness of the individual API particles' deagglomeration from the carrier particles. Since DPI particle transport is significantly affected by particle-particle interactions, particle sizes and shapes present significant challenges to CFD modelers to model regional lung deposition from a DPI. We employed the Particle-In-Cell method for studying the transport/deposition and the agglomeration and deagglomeration for DPI carrier and API particles in the present work. The proposed development will leverage CFD-PIC and sensitivity analysis capabilities from the Department of Energy laboratories: Multiphase Flow Interface Flow Exchange and Dakota UQ software. A data-driven framework is used to obtain the reliable low order statics of the particle's residence time in the inhaler. The framework is further used to study the effect of drug particle density, carrier particle density and size, fluidizing agent density and velocity, and some numerical parameters on the particles' residence time in the inhaler.

scholarly journals CFD DEM Analysis of a Dry Powder Inhaler

2019 ◽  
Author(s):  
Antara Badhan ◽  
V. M. Krushnarao Kotteda ◽  
Vinod Kumar
Keyword(s):  
Sensitivity Analysis ◽  
High Performance ◽  
Dry Powder Inhaler ◽  
Leading Edge ◽  
Active Pharmaceutical Ingredient ◽  
Department Of Energy ◽  
Discrete Element Modeling ◽  
Dry Powder ◽  
Throat Region ◽  
The Individual

Abstract 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.

Importance of Powder Residence Time for the Aerosol Delivery Performance of a Commercial Dry Powder Inhaler Aerolizer®

2012 ◽  
Vol 25 (5) ◽  
pp. 265-279 ◽  
Author(s):  
Liqun Jiang ◽  
Yue Tang ◽  
Hongjiu Zhang ◽  
Xifeng Lu ◽  
Xijing Chen ◽  
...  
Keyword(s):  
Residence Time ◽  
Dry Powder Inhaler ◽  
Aerosol Delivery ◽  
Dry Powder ◽  
Delivery Performance

Delivery of Dry Powders to the Lungs: Influence of Particle Attributes from a Biological and Technological Point of View

2019 ◽  
Vol 16 (3) ◽  
pp. 180-194 ◽  
Author(s):  
Sarah Zellnitz ◽  
Eva Roblegg ◽  
Joana Pinto ◽  
Eleonore Fröhlich
Keyword(s):  
Solid State ◽  
Dry Powder Inhaler ◽  
Point Of View ◽  
Dry Powder Inhalers ◽  
Dry Powder ◽  
Dry Powders ◽  
Pharmaceutical Ingredients ◽  
Technical Requirements ◽  
Particle Characteristics ◽  
Epithelial Cell Layer

Dry powder inhalers are medical devices used to deliver powder formulations of active pharmaceutical ingredients via oral inhalation to the lungs. Drug particles, from a biological perspective, should reach the targeted site, dissolve and permeate through the epithelial cell layer in order to deliver a therapeutic effect. However, drug particle attributes that lead to a biological activity are not always consistent with the technical requirements necessary for formulation design. For example, small cohesive drug particles may interact with neighbouring particles, resulting in large aggregates or even agglomerates that show poor flowability, solubility and permeability. To circumvent these hurdles, most dry powder inhalers currently on the market are carrier-based formulations. These formulations comprise drug particles, which are blended with larger carrier particles that need to detach again from the carrier during inhalation. Apart from blending process parameters, inhaler type used and patient’s inspiratory force, drug detachment strongly depends on the drug and carrier particle characteristics such as size, shape, solid-state and morphology as well as their interdependency. This review discusses critical particle characteristics. We consider size of the drug (1-5 µm in order to reach the lung), solid-state (crystalline to guarantee stability versus amorphous to improve dissolution), shape (spherical drug particles to avoid macrophage clearance) and surface morphology of the carrier (regular shaped smooth or nano-rough carrier surfaces for improved drug detachment.) that need to be considered in dry powder inhaler development taking into account the lung as biological barrier.

A generic fluticasone propionate and salmeterol dry powder inhaler: Evidence of usability, function, and robustness

2021 ◽  
Vol 42 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Donald P. Tashkin ◽  
Arkady Koltun ◽  
Róisín Wallace
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Fluticasone Propionate ◽  
Healthy Volunteers ◽  
Pulmonary Disease ◽  
Dry Powder Inhaler ◽  
Chemical Degradation ◽  
Chronic Obstructive ◽  
Dry Powder ◽  
Obstructive Pulmonary Disease ◽  
Flow Rates

Background: A generic combination of fluticasone propionate and salmeterol xinafoate inhalation powder in a premetered, multidose, nonreusable inhaler was recently approved. Objective: To assess the performance of the generic device. Methods: Findings from three studies with regard to device usability, function, and robustness were reviewed. Results: In a study to assess device function in patients and healthy volunteers, the generic device was successfully used by patients with asthma and chronic obstructive pulmonary disease who were either dry powder inhaler users or dry powder inhaler‐naive, even though they were not trained beyond being provided the instructions for use. In a study to measure inhaled flow rates generated by patients and healthy volunteers, the generic device consistently simulated the delivery of a full dose of drug, even to patients with severe respiratory disease and reduced inspiratory flow rates. Although the generic device had a slightly higher airflow resistance, this study demonstrated that this difference did not result in any clinically meaningful differences in terms of drug delivery. Pressure drop, a key parameter that drives the fluidization and aerosolization of the powder dose, was found to be comparable between the devices. In an open-label study, the generic device met all U.S. Food and Drug Administration specifications for device robustness after 21.5 days of twice-daily dosing via oral inhalation among 111 participants with asthma or chronic obstructive pulmonary disease. All inhalers tested demonstrated conformity with a pharmacopeia with respect to key quality parameters (assay, delivered dose uniformity, aerodynamic size distribution). There was no evidence of chemical degradation of the active ingredients, nor of microbial or water ingress into the powder, as a result of inhaler use.

scholarly journals Flow and Particle Modelling of Dry Powder Inhalers: Methodologies, Recent Development and Emerging Applications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 189
Author(s):  
Zhanying Zheng ◽  
Sharon Shui Yee Leung ◽  
Raghvendra Gupta
Keyword(s):  
Dry Powder Inhaler ◽  
Research Direction ◽  
Particle Methods ◽  
Future Research ◽  
High Dose ◽  
Dry Powder ◽  
Multi Scale ◽  
Wide Range ◽  
Computational Fluid Dynamics Cfd ◽  
Discrete Element Methods

Dry powder inhaler (DPI) is a device used to deliver a drug in dry powder form to the lungs. A wide range of DPI products is currently available, with the choice of DPI device largely depending on the dose, dosing frequency and powder properties of formulations. Computational fluid dynamics (CFD), together with various particle motion modelling tools, such as discrete particle methods (DPM) and discrete element methods (DEM), have been increasingly used to optimise DPI design by revealing the details of flow patterns, particle trajectories, de-agglomerations and depositions within the device and the delivery paths. This review article focuses on the development of the modelling methodologies of flow and particle behaviours in DPI devices and their applications to device design in several emerging fields. Various modelling methods, including the most recent multi-scale approaches, are covered and the latest simulation studies of different devices are summarised and critically assessed. The potential and effectiveness of the modelling tools in optimising designs of emerging DPI devices are specifically discussed, such as those with the features of high-dose, pediatric patient compatibility and independency of patients’ inhalation manoeuvres. Lastly, we summarise the challenges that remain to be addressed in DPI-related fluid and particle modelling and provide our thoughts on future research direction in this field.

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