Rational design of a dry powder inhaler: device design and optimisation (original) (raw)
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Experimental investigation of design parameters on dry powder inhaler performance
International Journal of Pharmaceutics, 2013
The study aims to investigate the impact of various design parameters of a dry powder inhaler on the turbulence intensities generated and the performance of the dry powder inhaler. The flow fields and turbulence intensities in the dry powder inhaler are measured using particle image velocimetry (PIV) techniques. In vitro aerosolization and deposition a blend of budesonide and lactose are measured using an Andersen Cascade Impactor. Design parameters such as inhaler grid hole diameter, grid voidage and chamber length are considered. The experimental results reveal that the hole diameter on the grid has negligible impact on the turbulence intensity generated in the chamber. On the other hand, hole diameters smaller than a critical size can lead to performance degradation due to excessive particle-grid collisions. An increase in grid voidage can improve the inhaler performance but the effect diminishes at high grid voidage. An increase in the chamber length can enhance the turbulence intensity generated but also increases the powder adhesion on the inhaler wall.
Journal of Pharmaceutical Sciences, 2004
This study investigates (1) the effect of modifying the design of a dry powder inhaler on the device performance, and (2) which design features significantly contribute to overall inhaler performance. Computational Fluid Dynamics (CFD) analysis was performed to determine how the flowfield generated in an Aerolizer 1 at 60 l min À1 varied when the inhaler grid and mouthpiece were modified. The computational models were validated by Laser Doppler Velocimetry (LDV). Dispersion performance of the modified inhalers was measured with a mannitol powder using a multistage liquid impinger at 60 l min À1 . The inhaler grid was found to significantly affect the performance of the Aerolizer 1 . As the grid voidage was increased, the amount of powder retained in the device doubled (due to increased tangential flow of particles in the inhaler mouthpiece) and the FPF Loaded was reduced from 57 to 44% (due to increased mouthpiece retention). The length of the mouthpiece played a lesser role on the inhaler performance, having no significant effect on the flowfield generated in the devices. In summary, the performance of a dry powder inhaler can be affected by simple design changes. CFD, coupled with experimental results, provides a rational basis for understanding the performance difference. ß Keywords: aerosols; pulmonary; targeted drug delivery; pulmonary drug delivery; computational modeling; dry powder inhaler; DPI; computational fluid dynamics; CFD Correspondence to: Hak-Kim Chan (Telephone: 61 (0)2 9351 3054; Fax: 61 (0)2 9351 4391;
Technological and practical challenges of dry powder inhalers and formulations
In the 50 years following the introduction of the first dry powder inhaler to the market, several developments have occurred. Multiple-unit dose and multi-dose devices have been introduced, but first generation capsule inhalers are still widely used for new formulations. Many new particle engineering techniques have been developed and considerable effort has been put in understanding the mechanisms that control particle interaction and powder dispersion during inhalation. Yet, several misconceptions about optimal inhaler performance manage to survive in modern literature. It is, for example still widely believed that a flow rate independent fine particle fraction contributes to an inhalation performance independent therapy, that dry powder inhalers perform best at 4 kPa (or 60 L/min) and that a high resistance device cannot be operated correctly by patients with reduced lung function. Nevertheless, there seems to be a great future for dry powder inhalation. Many new areas of interest for dry powder inhalation are explored and with the assistance of new techniques like computational fluid dynamics and emerging particle engineering technologies, this is likely to result in a new generation of inhaler devices and formulations, that will enable the introduction of new therapies based on inhaled medicines.
International journal of pharmaceutics, 2018
This work demonstrates the use of multi-scale simulations coupled with experiments to build a quantitative prediction tool for the performance of adhesive mixtures in a dry powder inhaler (DPI). Using discrete element model (DEM), the behaviour of fine-carrier particle assemblies upon different mechanisms encountered during dose entrainment and dispersion can be described at the individual particle level. Combining these results with computational fluid dynamics (CFD) simulations, the complete dosing event from a DPI can be captured and key performance measures can be extracted. A concept of apparent surface energy, ASE, was introduced to overcome challenges associated with the complex particle properties, e.g. irregular particle shapes and surface roughness. This approach correctly predicts trends observed experimentally regarding API adhesivity, flow rate and device geometry. By incorporating the effects of drug load, critical adhesion and surface energy distributions to the simul...
Development of Dry Powder Inhalers
Recent Patents on …, 2007
Development of dry powder inhalers involves powder recrystallization, formulation, dispersion, delivery, and deposition of the therapeutic agent in different regions of the airways in prophylaxis/ treatment/ diagnosis of pulmonary and systemic disorders. Conventional powder production by crystallization and milling has many limitations resulting into development of alternative techniques to overcome the problems. In the last decade many patents have been filed claiming improvement in aerosol performance of dry powder inhalers through the use of (i) incorporation of fines of carrier particles to occupy active sites on the surface and use of hydrophobic carriers to facilitate deaggregation through reduced surface energy and particle interaction (ii) reducing aerodynamic diameters through particle engineering and incorporating drug into porous or low particle density, and/or (iii) preparing less cohesive and adhesive particles through corrugated surfaces, low bulk density, reduced surface energy and particle interaction and hydrophobic additives. Moisture within dry powder inhaler (DPI) products has also been shown to influence aerosol performance via capillary force and electrostatic interaction. Better understanding of particle forces and surface energy has been achieved by the use of sophisticated analytical techniques. Understanding the intricacies of particle shape and surface properties influencing specific lung deposition has been further facilitated by the availability of newer and advanced softwares. A critical review of recent patents claiming different approaches to improve lung deposition of dry powder inhalers will help in deciding the focus of the research in the area of technological gaps.
Latest advances in the development of dry powder inhalers
Pharmaceutical Science & Technology Today, 2000
The current market for dry powder inhalers (DPIs) has over 20 devices in present use and at least another 30 under development. Clinicians recognize that DPIs are a suitable alternative to pressurized metered dose inhalers (pMDIs) for some patients but the relative performance of devices is often unclear. The problem is compounded by the need to reformulate pMDIs with new propellants, introducing further products to the market with associated variations in performance. This article reviews the DPIs currently available, the driving forces governing new designs, and the claimed advantages of DPIs in the development pipeline.
A method for the aerodynamic design of dry powder inhalers
International Journal of Pharmaceutics, 2011
An inhaler design methodology was developed and then used to design a new dry powder inhaler (DPI) which aimed to fulfill two main performance requirements. The first requirement was that the patient should be able to completely empty the dry powder from the blister in which it is stored by inspiratory effort alone. The second requirement was that the flow resistance of the inhaler should be geared to optimum patient comfort. The emptying of a blister is a two-phase flow problem, whilst the adjustment of the flow resistance is an aerodynamic design problem. The core of the method comprised visualization of fluid and particle flow in upscaled prototypes operated in water. The prototypes and particles were upscaled so that dynamic similarity conditions were approximated as closely as possible. The initial step in the design method was to characterize different blister prototypes by measurements of their flow resistance and particle emptying performance. The blisters were then compared with regard to their aerodynamic performance and their ease of production. Following selection of candidate blisters, the other components such as needle, bypass and mouthpiece were dimensioned on the basis of node-loop operations and validation experiments. The final shape of the inhaler was achieved by experimental iteration.
A REVIEW ON DEVELOPMENT OF DRY POWDER INHALER
A drug product combines pharmacologic activity with pharmaceutical properties. Desirable performance characteristics are physical and chemical stability, ease of processing, accurate and reproducible delivery to the target organ, and availability at the site of action. For the dry powder inhaler (DPI), these goals can be met with a suitable powder formulation, an efficient metering system, and a carefully selected device. This review focuses on the DPI formulation and development process. Most DPI formulations consist of micronized drug blended with larger carrier particles, which enhance flow, reduce aggregation, and aid in dispersion. A combination of intrinsic physicochemical properties, particle size, shape, surface area, and morphology affects the forces of interaction and aerodynamic properties, which in turn determine fluidization, dispersion, delivery to the lungs, and deposition in the peripheral airways. When a DPI is actuated, the formulation is fluidized and enters the patient's airways. Under the influence of inspiratory airflow, the drug particles separate from the carrier particles and are carried deep into the lungs, while the larger carrier particles impact on the oropharyngeal surfaces and are cleared. If the cohesive forces acting on the powder are too strong, the shear of the airflow may not be sufficient to separate the drug from the carrier particles, which results in low deposition efficiency.
Predicting extrathoracic deposition from dry powder inhalers
Journal of Aerosol Science, 2004
The deposition of monodisperse aerosols entering an idealized oral cavity geometry through a variety of inlets was experimentally measured. Aerosol particles with diameters of 2.5, 3.8 and 5:0 m were investigated at ow rates ranging from 15 to 90 L=min. The tested inlets ranged in diameter from 3 to 17 mm and included contraction nozzles, straight tubes, a turbulence generator and six commercially available dry powder inhalers (DPIs). A model for predicting the oral cavity deposition was derived from the data based on the particle Stokes number near the primary impaction location modiÿed to incorporate the turbulent kinetic energy at the inlet. The model predicted similar (but slightly underestimated) deposition for monodisperse aerosols entering through DPIs, with increasing deposition for decreasing inlet diameter. The model was then extended to predict extrathoracic deposition for polydisperse aerosol formulations in vivo. Improved agreement was found between the in vitro predictions and the in vivo measurements compared to previous attempts. ?
Dry powder inhaler device influence on carrier particle performance
Journal of …, 2012
Dry powder inhalers (DPIs) are distinguished from one another by their unique device geometries, reflecting their distinct drug detachment mechanisms, which can be broadly classified into either aerodynamic or mechanical-based detachment forces. Accordingly, powder particles experience different aerodynamic and mechanical forces depending on the inhaler. However, the influence of carrier particle physical properties on the performance of DPIs with different dispersion mechanisms remains largely unexplored. Carrier particle trajectories through two commercial DPIs were modeled with computational fluid dynamics (CFD) and the results were compared with in vitro aerosol studies to assess the role of carrier particle size and shape on inhaler performance. Two percent (w/w) binary blends of budesonide with anhydrous and granulated lactose carriers ranging up to 300 :m were dispersed from both an Aerolizer R and Handihaler R through a cascade impactor at 60 L min −1 . For the simulations, carrier particles were modeled as spherical monodisperse populations with small (32 :m), medium (108 :m), and large (275 :m) particle diameters. CFD simulations revealed the average number of carrier particle-inhaler collisions increased with carrier particle size (2.3-4.0) in the Aerolizer R , reflecting the improved performance observed in vitro. Collisions within the Handihaler R , in contrast, were less frequent and generally independent of carrier particle size. The results demonstrate that the aerodynamic behavior of carrier particles varies markedly with both their physical properties and the inhalation device, significantly influencing the performance of a dry powder inhaler formulation.