Potential of a Cyclone Prototype Spacer to Improve In Vitro Dry Powder Delivery

Purpose

Low inspiratory force in patients with lung disease is associated with poor deagglomeration and high throat deposition when using dry powder inhalers (DPIs). The potential of two reverse flow cyclone prototypes as spacers for commercial carrier-based DPIs was investigated.

Methods

Cyclohaler®, Accuhaler® and Easyhaler® were tested with and without the spacers between 30 and 60 Lmin^?1. Deposition of particles in the next generation impactor and within the devices was determined by high performance liquid chromatography.

Results

Reduced induction port deposition of the emitted particles from the cyclones was observed due to the high retention of the drug within the spacers (e.g. salbutamol sulphate (SS): 67.89?±?6.51% at 30 Lmin^?1 in Cheng 1). Fine particle fractions of aerosol as emitted from the cyclones were substantially higher than the DPIs alone. Moreover, the aerodynamic diameters of particles emitted from the cyclones were halved compared to the DPIs alone (e.g. SS from the Cyclohaler® at 4 kPa: 1.08?±?0.05 μm vs. 3.00?±?0.12 μm, with and without Cheng 2, respectively) and unaltered with increased flow rates.

Conclusion

This work has shown the potential of employing a cyclone spacer for commercial carrier-based DPIs to improve inhaled drug delivery.     

Dose emissions from marketed dry powder inhalers

The dose emission characteristics of eight marketed dry powder inhalers (DPIs: Intal Spinhaler®, Ventolin and Becotide Diskhalers®, Ventolin and Becotide Rotahalers®, Bricanyl and Pulmicort Turbohalers®, Berotec Inhalator® have been investigated using the proposed USP dosage unit sampling apparatus for DPIs. Intra- and inter-device variation in emitted doses was determined at air flow rates of 60 and 100 1/min using a 4 1 air throughput in each case except Inhalator®, which was tested at 30 l/min only. The sampling apparatus was found to be suitable for quantifying single emitted doses from all of these devices which comprise examples of low, medium and high airflow resistance DPIs (Table 1 footnote). Dose emissions from the DPIs are presented as percentages of the manufacturers' label claims. Under all test flow conditions variability was high, when compared to the uniformity of content standards usually applied to pharmaceutical products; in some cases relative standard deviations (RSD) were greater than 15%, both within and between devices. However, under the proposed USP test flow rate conditions, the total RSD (n = 25) was < 15% around the average emitted dose in all cases except Pulmicort Turbohaler®; such variance (RSD< 15%) is proposed to be acceptable for DPIs delivering current medications. Only the Intal Spinhaler® emitted an average dose similar to its label claim. Testing at 100 1/min vs 60 1/min significantly increased DPI drug emission and reduced the device retention of both the Ventolin® and Becotide® versions of the low resistance devices, Rotahaler® and Diskhaler®. Using these same flow rates for testing the dose emissions from the medium resistance Bricanyl and Pulmicort Turbohalers®, there was no significant difference in drug output between the two flow rates.     

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

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.     

Development of a High Efficiency Dry Powder Inhaler: Effects of Capsule Chamber Design and Inhaler Surface Modifications

Purpose

The objective of this study was to explore the performance of a high efficiency dry powder inhaler (DPI) intended for excipient enhanced growth (EEG) aerosol delivery based on changes to the capsule orientation and surface modifications of the capsule and device.

Methods

DPIs were constructed by combining newly designed capsule chambers (CC) with a previously developed three-dimensional (3D) rod array for particle deagglomeration and a previously optimized EEG formulation. The new CCs oriented the capsule perpendicular to the incoming airflow and were analyzed for different air inlets at a constant pressure drop across the device. Modifications to the inhaler and capsule surfaces included use of metal dispersion rods and surface coatings. Aerosolization performance of the new DPIs was evaluated and compared with commercial devices.

Results

The proposed capsule orientation and motion pattern increased capsule vibrational frequency and reduced the aerosol MMAD compared with commercial/modified DPIs. The use of metal rods in the 3D array further improved inhaler performance. Coating the inhaler and capsule with PTFE significantly increased emitted dose (ED) from the optimized DPI.

Conclusions

High efficiency performance is achieved for EEG delivery with the optimized DPI device and formulation combination producing an aerosol with MMAD?<?1.5 μm, FPF_<5μm/ED?>?90%, and ED?>?80%.     

Importance of powder residence time for the aerosol delivery performance of a commercial dry powder inhaler aerolizer(®)

Abstract Background: The performance of dry powder aerosol delivery systems depends not only on the powder formulation but also on the dry powder inhalers (DPIs). Effects of turbulence, grid, mouthpiece, inlet size, air flow, and capsule on the DPIs performance have been investigated previously. Considering powder dispersion in DPIs is a time-dependent process, the powder residence time in DPIs is supposed to have a great impact on DPIs efficiency. This study sought to investigate the effect of powder residence time on the performance of a commercial DPI Aerolizer(?). Methods: A standard Aerolizer(?) (SD) and five modified devices (MD1, MD2, MD3, MD4, and MD5) were employed for this research. Computational fluid dynamics analysis was used to calculate the flow field and the powder residence time in these devices. Recombinant human interleukin-2 inhalation powders and a twin impinger were used for the deposition experiment. Results: The powder mean residence time in the secondary atomization zone of the devices was increased from 0?ms for SD to 0.33, 0.96, 1.42, 1.76, and 2.14?ms for MD1, MD2, MD3, MD4, and MD5, respectively. At a flow rate of 60?L/min, with an increase in the powder residence time in these devices, a significant gradual and increasing trend in the powder respirable fraction was observed from 29.1%±1.1% (MD1) to 32.6%±2.2% (MD2), 37.1%±1.1% (MD3), and 43.7%±2.1% (MD4). There was no significant difference in the powder respirable fraction between SD and MD1 or between MD4 and MD5. Conclusions: Within a certain range, increasing the powder residence time could improve the performance of Aerolizer(?) by increasing the powder-air interaction time (the main reason) and increasing the powder-device compaction (the secondary reason). Combination of high turbulence level and sufficient powder residence time could further improve the device performance.     

Influence of Air Flow on the Performance of a Dry Powder Inhaler Using Computational and Experimental Analyses

Purpose The aims of the study are to analyze the influence of air flow on the overall performance of a dry powder inhaler (Aerolizer^®) and to provide an initial quantification of the flow turbulence levels and particle impaction velocities that maximized the inhaler dispersion performance.Methods Computational fluid dynamics (CFD) analysis of the flowfield in the Aerolizer^®, in conjunction with experimental dispersions of mannitol powder using a multistage liquid impinger, was used to determine how the inhaler dispersion performance varied as the device flow rate was increased.Results Both the powder dispersion and throat deposition were increased with air flow. The capsule retention was decreased with flow, whereas the device retention first increased then decreased with flow. The optimal inhaler performance was found at 65 l min⁻¹ showing a high fine particle fraction (FPF) of 63 wt.% with low throat deposition (9.0 wt.%) and capsule retention (4.3 wt.%). Computational fluid dynamics analysis showed that at the critical flow rate of 65 l min⁻¹, the volume-averaged integral scale strain rate (ISSR) was 5,400 s⁻¹, and the average particle impaction velocities were 12.7 and 19.0 m s⁻¹ at the inhaler base and grid, respectively. Correlations between the device flow rate and (a) the amount of throat deposition and (b) the capsule emptying times were also developed.Conclusions The use of CFD has provided further insight into the effect of air flow on the performance of the Aerolizer^®. The approach of using CFD coupled with powder dispersion is readily applicable to other dry powder inhalers (DPIs) to help better understand their performance optimization.     

The Delivery of High-Dose Dry Powder Antibiotics by a Low-Cost Generic Inhaler

The routine of loading multiple capsules for delivery of high-dose antibiotics is time consuming, which may reduce patient adherence to inhaled treatment. To overcome this limitation, an investigation was carried out using four modified versions of the Aerolizer® that accommodate a size 0 capsule for delivery of high payload formulations. In some prototypes, four piercing pins of 0.6 mm each were replaced with a single centrally located 1.2-mm pin and one-third reduced air inlet of the original design. The performance of these inhalers was evaluated using spray-dried antibiotic powders with distinct morphologies: spherical particles with a highly corrugated surface (colistin and tobramycin) and needle-like particles (rifapentine). The inhalers were tested at capsule loadings of 50 mg (colistin), 30 mg (rifapentine) and 100 mg (tobramycin) using a multistage liquid impinger (MSLI) operating at 60 L/min. The device with a single pin and reduced air inlet showed a superior performance than the other prototypes in dispersing colistin and rifapentine powders, with a fine particle fraction (FPF wt% <5 μm in the aerosol) between 62 and 68%. Subsequently, an Aerolizer® with the same configuration (single pin and one-third air inlet) that accommodates a size 00 capsule was designed to increase the payload of colistin and rifapentine. The performance of the device at various inspiratory flow rates and air volumes achievable by most cystic fibrosis (CF) patients was examined at the maximum capsule loading of 100 mg. The device showed optimal performance at 45 L/min with an air volume of 1.5–2.0 L for colistin and 60 L/min with an air volume of 2.0 L for rifapentine. In conclusion, the modified size 00 Aerolizer® inhaler as a low-cost generic device demonstrated promising results for delivery of various high-dose formulations for treatment of lung infections.     

Development and Comparison of New High-Efficiency Dry Powder Inhalers for Carrier-Free Formulations

High-efficiency dry powder inhalers (DPIs) were developed and tested for use with carrier-free formulations across a range of different inhalation flow rates. Performance of a previously reported DPI was compared with two new designs in terms of emitted dose (ED) and aerosolization characteristics using in vitro experiments. The two new designs oriented the capsule chamber (CC) at different angles to the main flow passage, which contained a three-dimensional (3D) rod array for aerosol deaggregation. Computational fluid dynamics simulations of a previously developed deaggregation parameter, the nondimensional specific dissipation (NDSD), were used to explain device performance. Orienting the CC at 90° to the mouthpiece, the CC₉₀-3D inhaler provided the best performance with an ED = 73.4%, fine particle fractions (FPFs) less than 5 and 1 μm of 95.1% and 31.4%, respectively, and a mass median aerodynamic diameter (MMAD) = 1.5 μm. For the carrier-free formulation, deaggregation was primarily influenced by capsule aperture position and the NDSD parameter. The new CC-3D inhalers reduced the percent difference in FPF and MMAD between low and high flows by 1–2 orders of magnitude compared with current commercial devices. In conclusion, the new CC-3D inhalers produced extremely high-quality aerosols with little sensitivity to flow rate and are expected to deliver approximately 95% of the ED to the lungs.     

Novel approach for real-time monitoring of carrier-based DPIs delivery process via pulmonary route based on modular modified Sympatec HELOS

An explicit illustration of pulmonary delivery processes (PDPs) was a prerequisite for the formulation design and optimization of carrier-based DPIs. However, the current evaluation approaches for DPIs could not provide precise investigation of each PDP separately, or the approaches merely used a simplified and idealized model. In the present study, a novel modular modified Sympatec HELOS (MMSH) was developed to fully investigate the mechanism of each PDP separately in real-time. An inhaler device, artificial throat and pre-separator were separately integrated with a Sympatec HELOS. The dispersion and fluidization, transportation, detachment and deposition processes of pulmonary delivery for model DPIs were explored under different flow rates. Moreover, time-sliced measurements were used to monitor the PDPs in real-time. The Next Generation Impactor (NGI) was applied to determine the aerosolization performance of the model DPIs. The release profiles of the drug particles, drug aggregations and carriers were obtained by MMSH in real-time. Each PDP of the DPIs was analyzed in detail. Moreover, a positive correlation was established between the total release amount of drug particles and the fine particle fraction (FPF) values (R² = 0.9898). The innovative MMSH was successfully developed and was capable of illustrating the PDPs and the mechanism of carrier-based DPIs, providing a theoretical basis for the design and optimization of carrier-based DPIs.     

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

Purpose

We hypothesize that the USP induction port may de-agglomerate carrier-free powder emitting from dry powder inhalers (DPIs).

Methods

Aerosols emitting from a range of DPIs (Spinhaler^?, Turbuhaler^? and Osmohaler^TM) 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).

Results

The 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.

Conclusion

The 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.     

The effect of inspiratory parameters after two separate inhalations on the dose emission of theophylline from low and high resistance dry powder inhalers

The dose emission from DPIs can be affected by the inspiratory parameters achieved by the patient as well as the device in-use. Conventional in-vitro dose emission methodology was used, but instead of using inhalation volume (Vin) of 2 or 4 L and peak inhalation flow (PIF) corresponding to 4 kPa, a range of PIFs (28.3, 60, 90 and 120 L min⁻¹) and Vins (0.5, 0.75, 1, 1.5, 2, and 4 L) were used. The formulation was composed of spray dried Theophylline as a model drug with Lactohale® α lactose monohydrate carrier. The formulation was aerosolised using two DPIs; a low resistance Breezhaler® and high resistance Handihaler®. The formulation showed a consistent dose content uniformity with a Coefficient of Variation (CV) of 1.70%. The drug distribution on the surface of the carrier was obvious from the SE micrographs with some drug particles lodged into lactose crevices. The dose emission after the first inhalation (ED1) and total emitted dose (TED) of theophylline increased with PIF and Vin, irrespective of the inhaler device. However, the dose delivered was superior for the Handihaler® compared to Breezhaler®. Drug retention in the capsule and device was high at low PIFs and Vins and reduced after the second inhalation. Therefore, our study supports the recommendations for patients who cannot achieve sufficient PIF and Vin to inhale twice for each dose to ensure the better clinical outcome.     

Effect of Device Design on the In Vitro Performance and Comparability for Capsule-Based Dry Powder Inhalers

This study investigated the effect of modifying the design of the Cyclohaler on its aerosolization performance and comparability to the HandiHaler at multiple flow rates. The Cyclohaler and HandiHaler were designated as model test and reference unit-dose, capsule-based dry powder inhalers (DPIs), respectively. The flow field, pressure drop, and carrier particle trajectories within the Cyclohaler and HandiHaler were modeled via computational fluid dynamics (CFD). With the goal of achieving in vitro comparability to the HandiHaler, the CFD results were used to identify key device attributes and to design two modifications of the Cyclohaler (Mod 1 and Mod 2), which matched the specific resistance of the HandiHaler but exhibited different cyclonic flow conditions in the device. Aerosolization performance of the four DPI devices was evaluated by using the reference product''s capsule and formulation (Spiriva capsule) and a multistage cascade impactor. The in vitro data showed that Mod 2 provided a closer match to the HandiHaler than the Cyclohaler and Mod 1 at 20, 39, and 55 l/min. The in vitro and CFD results together suggest that matching the resistance of test and reference DPI devices is not sufficient to attain comparable aerosolization performance, and the improved in vitro comparability of Mod 2 to the HandiHaler may be related to the greater degree of similarities of the flow rate of air through the pierced capsule (Q_c) and the maximum impact velocity of representative carrier particles (V_n) in the Cyclohaler-based device. This investigation illustrates the importance of enhanced product understanding, in this case through the CFD modeling and in vitro characterization of aerosolization performance, to enable identification and modification of key design features of a test DPI device for achieving comparable aerosolization performance to the reference DPI device.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-012-9379-9) contains supplementary material, which is available to authorized users.KEY WORDS: computational fluid dynamics, device design, dry powder inhaler, in vitro comparability, in vitro performance     

The Effect of Altitude on Inhaler Performance

The purpose of the study is to understand the effect of altitude on the performance of selected pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). A testing apparatus that created consistent breath profiles through the Alberta Idealized Throat was designed to test five pMDIs and two DPIs at altitudes of 670, 2450, 3260, and 4300 m. Both gravimetric and chemical assays were conducted to determine the in vitro lung dose. Additionally, spray duration and shot weight for pMDIs and device resistance for DPI were measured. There was no significant change in in vitro lung dose for any of the pMDIs tested. Shot weight and spray duration were unaffected. The device resistance of the DPIs decreased with increasing altitude and was successfully modeled as a function of ambient pressure. The in vitro lung dose of both DPIs showed no significant change when operated with an inhaler pressure drop of 4 kPa, but for the Bricanyl® Turbuhaler®, a significant decrease occurred when matching the volumetric inspiratory flow rate to that of the baseline altitude. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2116–2124, 2014     

State of the art and new perspectives on dry powder inhalers

Modern local therapy for lung diseases is now largely based on pressurized metered-dose inhalers (MDIs). The research of alternatives to MDIs has recently accelerated, primarily due to environmental concerns related to the use of chlorofluorocarbon (CFC) propellants. The most recent and attractive solution to this problem is represented by the development of dry powder inhalers (DPIs), particularly designed to avoid the use of propellants. DPIs have been developed for specific products, therefore they possess a reduced versatility in term of application of the same device to different drugs. However, they did introduce new concepts in pulmonary drug delivery, solving some disadvantages of the pressurized devices. They are in their infancy and the efforts of researchers are now impressive. The future will certainly see many other devices containing additional innovative features for the effective respiratory delivery of drug. The goals still remain the delivery of precise and uniform drug doses and increasing the respirable fraction in relation to the dose emitted from the device.     

The Acoustic Features of Inhalation can be Used to Quantify Aerosol Delivery from a Diskus™ Dry Powder Inhaler

Purpose

Some patients are unable to generate the peak inspiratory flow rate (PIFR) necessary to de-agglomerate drug particles from dry powder inhalers (DPIs). In this study we tested the hypothesis that the acoustic parameters of an inhalation are related to the PIFR and hence reflect drug delivery.

Methods

A sensitivity analysis of the relationship of the acoustics of inhalation to simultaneously recorded airflow, in a cohort of volunteers (n?=?92) was performed. The Next Generation Impactor (NGI) was used to assess in vitro drug delivery from salmeterol/fluticasone and salbutamol Diskus? DPIs. Fine particle fraction, FPF, (<5 μm) was measured at 30–90 l/min for 2–6 s and correlated with acoustically determined flow rate (IFRc). In pharmacokinetic studies using a salbutamol (200 μg) Diskus?, volunteers inhaled either at maximal or minimal effort on separate days.

Results

PIFRc was correlated with spirometrically determined values (R ²?=?0.88). In in vitro studies, FPF increased as both flow rate and inhalation duration increased for the salmeterol/fluticasone Diskus? (Adjusted R ²?=?0.95) and was proportional to flow rate only for the salbutamol Diskus? (Adjusted R ²?=?0.71). In pharmacokinetic studies, blood salbutamol levels measured at 20 min were significantly lower when PIFRc was less than 60 l/min, p?Conclusion Acoustically-determined PIFR is a suitable method for estimating drug delivery and for monitoring inhalation technique over time.     

粉雾剂装置气流阻力与药物分散行为的关系

目的 研究不同分散机制的粉雾剂装置气流阻力与载体型制剂粉末分散行为间的关系。方法 以Lactohale 206^®与马来酸氯苯那敏（CPM）混合粉末为制剂模型,4款不同阻力的吸入器为吸入装置： RS01-L、RS01-M、RS01-H、Handihaler^®（HD）,借助计算流体力学（CFD）、离散相（DPM）、离散元（DEM）方法,探讨在30、60 L/min 2种体积流量下,制剂载体颗粒在不同阻力装置内的运动、分散情况;同时,运用新一代撞击器（NGI）研究模型制剂在2种体积流量下、通过不同装置后的体外沉积表现,并与数值模拟结果进行比较、分析。结果 CFD结果表明,装置气流阻力及气流流量均对装置内流场强度有影响,当装置内体积流量提高时,结构类似的RS01-L、RS01-H的装置湍流动能变化集中于旋转腔及格栅处区域,可能会影响胶囊从装置中的递送;而HD装置胶囊仓吸嘴等部件流场紊乱程度均提高。DPM结果表明,载体颗粒在装置内的运动速度随装置阻力及流量提高而增加,对RS01-L、RS01-H类结构而言,流量提高主要促进载体在分散腔内的运动速度,增加颗粒与装置的碰撞次数;HD装置内载体颗粒流量虽提高,但颗粒运动轨迹差异不明显;DEM结果表明,相同体积流量下,RS01系列的L、H装置气流-颗粒相对速度平方值远低于HD装置,HD装置中气流剪切作用强于同等体积流量下RS01装置,HD装置总碰撞能量损失远低于RS01。体外实验结果表明,RS01系列的L、M、H装置递送剂量（DD）受体积流量影响较小;HD装置内体积流量越高,装置残留和胶囊残留越低,DD越大;装置残留RS01系列明显高于HD,且随气流体积流量的升高,L、M装置残留降低显著（P<0.05、0.001）;HD装置体积流量提高后,预分离器药物残留显著降低（P<0.001）,但颗粒在惯性作用下在喉管的残留则显著增加（P<0.001）;RS01系列装置在2种体积流量下喉部沉积无显著性差异,高流量下H装置预分离器沉积较低流速显著增加（P<0.001）;2种体积流量下,微细粒子剂量（FPD）均随RS01系列装置阻力增加而显著提高（P<0.05、0.01、0.001）,质量中值空气动力学粒径（MMAD）均随装置阻力增加呈下降趋势;RS01系列装置分散药物能力随体积流量增高而显著提高（P<0.001）;而对HD装置而言,体积流量增加后,MMAD虽降低,分散能力有所提升,但FPD变化不明显。结论 装置气流阻力是调节装置分散性能的一种可行的方式,体积流量一致时,装置阻力增加（通常由截面积变小造成）,气流流速提高,制剂粉末颗粒运动速度升高,颗粒与装置壁面的碰撞作用增强,粉末分散效果得到提升,从而改善了药物分散、沉积表现。     

吸入粉雾剂工程颗粒技术研究

对于吸入粉雾剂来说,由于活性药物成分（API）较小的粒径和较高的表面能,导致微粉易于团聚,难以分散。微粒间的内聚力和微粒与乳糖间的粘附力导致粉雾剂产品较低的微细粒子比例（FPF）。通过工程颗粒可以改善API微粒的物化性质,进而显著提高DPI产品的递送效率。概述通过工程颗粒的制备API微粉的方法,包括反溶剂结晶、湿法粉碎/研磨、喷雾/冷冻干燥、超临界流体等方法,可以显著提高粉雾剂的雾化性能。     

Novolizer: how does it fit into inhalation therapy?

Inhalation therapy is the preferred route of administration of anti-asthmatic drugs to the lungs. However, the vast majority of patients cannot use their inhalers correctly, particularly pressurised metered dose inhalers (pMDIs). The actual proportion of patients who do not use their inhalers correctly may even be under-estimated as GPs tend to over-estimate correct inhalation technique. Dry powder inhalers (DPIs) have many advantages over pMDIs. Unlike pMDIs, they are environmentally-friendly, contain no propellant gases and, more importantly, they are breath-activated, so that the patient does not need to coordinate actuation of the inhaler with inspiration. Three key parameters for correct inhaler use should be considered when evaluating existing or future DPI devices and especially when choosing the appropriate device for the patient: (1) usability, (2) particle size distribution of the emitted drug and (3) intrinsic airflow resistance of the device. The Novolizer is a breath-activated, multidose, refillable DPI. It is easy to use correctly, has multiple feedback and control mechanisms which guide the patient through the correct inhalation manoeuvre. In addition, the Novolizer has an intelligent dose counter, which resets only after a correct inhalation and may help to monitor patient compliance. The Novolizer has a comparable or better lung deposition than the Turbuhaler at similar or higher peak inspiratory flow (PIF) rates. A flow trigger valve system ensures a clinically effective fine particle fraction (FPF) and sufficient drug delivery, which is important for a good lung deposition. The FPF produced through the Novolizer is also relatively independent of flow rate and the device shows better reproducibility of metering and delivery performance compared to the Turbuhaler. The low-to-medium airflow resistance means that the Novolizer is easy for patients to use correctly. Even children, patients with severe asthma and patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) have no problems to generate the trigger inspiratory flow rate required to activate the Novolizer. The Novolizer uses an advanced DPI technology and may improve patient compliance.     

Effect of design on the performance of a dry powder inhaler using computational fluid dynamics. Part 1: Grid structure and mouthpiece length

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 at 60 l min(-1) 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(-1). The inhaler grid was found to significantly affect the performance of the Aerolizer. 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.