Influence of particle size and patient dosing technique on lung deposition of HFA-beclomethasone from a metered dose inhaler.

The objective of this study was to determine the lung delivery of HFA-134a-beclomethasone dipropionate (HFA-BDP) from a breath-activated inhaler (QVAR Autohaler) compared with proper and improper press and breathe (QVAR P&B) metered dose inhaler (MDI) technique. The hypothesis was that that the smaller particles of BDP from HFA-BDP would stay suspended longer in the inspiratory air of patients and thus reduce the deleterious effects of inhaler discoordination. The study was an open label, four period, cross-over design. Asthmatic patients (n = 7) with a history of asthma symptoms, an FEV-1 of >70% of predicted normal, and a history of reversibility to a beta-agonist of >or=12% were utilized. BDP was radiolabeled with technetium-99m and delivered from the QVAR Autohaler or QVAR P&B device in patients trained to reproducibly utilize coordinated and discoordinated P&B MDI technique. Patients using Autohaler MDI exhibited 60% lung deposition of BDP. Patients using coordinated technique with the P&B MDI exhibited 59% lung deposition. Patients trained to consistently actuate the P&B MDI before inhaling exhibited 37% lung deposition. Patients trained to consistently actuate the P&B MDI late in the inspiration (i.e., 1.5 sec into a 3-sec inspiration) exhibited 50% lung deposition. In conclusion, the breath-activated Autohaler automatically provided optimal BDP lung deposition of 60%. Patients with good P&B MDI technique also received optimal lung deposition of 59%. The degree of lung deposition was decreased as patients demonstrated poor inhaler technique. However patients with poor technique still received a large lung dose of BDP (i.e., >or=37%) compared with lung deposition values of 4-7% for CFC-BDP MDIs previously published and confirmed in this study.     

Mass output and particle size distribution of glucocorticosteroids emitted from different inhalation devices depending on various inspiratory parameters.

Efficient inhalation therapy depends on successful delivery of the drug to the lung. The efficacy of drug delivery is not only influenced by the characteristics of the inhalation device, but also by the patient's handling of the device and by the inspiratory maneuver achieved through the device. We analyzed the output characteristics of three different chlorofluorocarbon (CFC)-free breath-actuated inhalers for inhaled glucocorticosteroids (BUD Turbohaler, FP Diskus/Accuhaler and HFA-BDP Autohaler, respectively). Mass output and particle size distribution of drug aerosol delivered by the inhalers were determined depending on different inhalation parameters in vitro using an Andersen cascade impactor. We found that, beside the peak inspiratory flow (PIF), other factors such as flow acceleration and inhalation volume also have significant effects on aerosol generation with respect to mass output and particle size distribution. Thus, these parameters should be taken into account when a suitable device for an individual patient is to be selected. The dependency on inspiratory parameters was most pronounced for the dry powder inhalers. The Turbohaler showed by far the highest variance in particle output (fine particle fraction ranging from 3.4% to 22.1% of label claim), whereas the Diskus was less dependent on variations in inhalation (10.6% to 18.5% of label claim). The most constant aerosol output was found for the Autohaler, which also released the highest fine particle fraction (43.1% to 56.6% of label claim).     

Pulmonary drug delivery from the Taifun dry powder inhaler is relatively independent of the patient's inspiratory effort.

The Taifun dry powder inhaler (Leiras OY, Turku, Finland) is a breath-actuated, multidose device, each metered dose containing 200 micrograms of budesonide. A two-way randomized crossover gamma scintigraphic study was performed in 10 asthmatic patients to determine the in vivo deposition pattern of budesonide inhaled from the Taifun. In vitro radiolabelling validation studies demonstrated that the radiolabel could be used as an accurate marker to assess in vivo drug deposition. Patients used either maximal inspiratory effort (targeted peak inhalation flow 30 L/min) or submaximal inspiratory effort (targeted peak inhalation flow 15 L/min) on each study day. Mean (S.D.) whole lung deposition (% of metered dose) was 34.3 (5.8)% and 29.6 (5.9)% for the two inhalation flows. The intersubject coefficient of variation in lung deposition was less than 20% on both study days. Drug was deposited uniformly across the central, intermediate, and peripheral lung regions for maximal and submaximal inspiratory efforts. The study suggests that the Taifun is a superior drug delivery device compared with many other inhalers, in terms of the amount of drug deposited in the lungs, the reproducibility of the lung dose, and the relative flow--independence of lung deposition.     

The inhalation manager: a new computer-based device to assess inhalation technique and drug delivery to the patient.

The rational choice of an inhalation device is a cornerstone in the effective management of asthma and COPD. In this publication, we describe the development of a new system, the Inhalation Manager, which, for the first time, offers the possibility to assess the entire inhalation maneuver of patients using original devices under everyday conditions. So far the Inhalation Manager allows the measurement of inspiratory maneuvers of patients through placebo inhalation devices of the most common breath-actuated CFC-free inhalers in the market for the three main glucocorticosteroids Budesonide [Turbohaler (TH), dry powder inhaler (DPI)], Beclomethasone dipropionate [Autohaler (AH), breath-actuated pressurized metered dose inhaler (pMDI)], and Fluticasone propionate [Diskus (DI), DPI] by means of a pneumotachometer. In addition, it allows allocation of the individual maneuver to the expected drug delivery values (mass output and particle size distribution) of these three devices. In a field trial, the inhalation technique of 628 (TH), 794 (AH), and 795 (DI) patients, respectively, was tested in 72 pulmonologist practices with the Inhalation Manager. For patients in the 18-59-year-old group, the Inhalation Manager detected the following percentages needing improvement: 1.5% for the Autohaler device, 16.7% for the Diskus, and 38.9% for the Turbohaler. In the 60-99-year-old group, percentages needing improvement were 1.5%, 31.5%, and 66.1% for the Autohaler, Diskus, and Turbohaler, respectively. Therefore, the Inhalation Manager could become an essential tool in asthma management by finding the most suitable inhaler for an individual patient and by training the optimal inhalation technique.     

Rationale for the choice of an aerosol delivery system.

The choice of an aerosol delivery system depends on numerous factors such as the drug itself, the characteristics of the aerosol generator, the patient and his or her disease, the physician, and the clinical setting, notably an emergency situation or not. Some rules always apply: an ultrasonic nebulizer should not be used to aerosolize a drug suspension; whenever possible, the same type of aerosol generator should be used for all inhaled medications received by a given patient; for outpatients, education is a major factor to ensure treatment efficacy. When the deposition of the aerosolized drug is aimed at the terminal respiratory units, nebulizers that generate micronic aerosols should be chosen. When the deposition of the aerosolized drug is aimed at the conducting airways, the metered dose inhaler (MDI) is the first choice. However, the MDI is often ill-used, notably in children and elderly people. Therefore, other inhalation devices have been developed: spacers, dry-powder inhalers, breath-actuated MDIs and, more recently, piezo-electric devices. They have been shown to increase lung deposition of drugs in poor coordinators but they all have limitations, which may affect their clinical efficacy. These limitations include the cumbersome dimensions of spacers, the dependency of lung deposition of dry powders on the inspiratory flow rate, the need for reformulation of breath-actuated or not MDIs with CFC-free gases. Nebulization of drugs should be considered only when no portable device is available for the considered drug, or in case of failure of other forms of aerosol administration.     

Effect of inhalation flow rate on the dosing characteristics of dry powder inhaler (DPI) and metered dose inhaler (MDI) products.

Both the dose delivered from the device and the particle size of the medication are important parameters for inhalation products because they influence the amount of drug that is delivered to the patient's lung. The inspiratory flow rate may vary from dose to dose in a given patient and between patients. The Marple-Miller Cascade Impactor, a new multistage inertial impactor that operates at two flow rates (30 and 60 liters/min) with comparable particle size cut-offs, provides a means to study the effect of inhalation flow rate on the particle size distributions of inhalation products. The medication delivery, mass median aerodynamic diameter (MMAD), and fine particle mass were determined, in a randomized fashion, for albuterol, beclomethasone, budesonide, and terbutaline in both metered dose inhaler (MDI) and dry powder inhaler (DPI) products as a function of flow rate. In all cases, independent of drug or device used, the MDI products had a more reproducible respirable dose than the breath-actuated DPI products tested as a function of inhalation flow rate.     

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.     

How to achieve good compliance and adherence with inhalation therapy

The correct use of inhaler devices is an inclusion criterion for all studies comparing inhaled treatments. However, in real life patients make many errors when inhaling their medication which may negate the benefits observed in clinical trials. A recently published observational study evaluated inhaler handling in 3811 patients for at least 1 month using the Aerolizer, Autohaler, Diskus, pressurised metered dose inhaler (pMDI) or Turbuhaler devices. Inhalation errors were considered critical if they could have substantially affected drug delivery to the lung. The two most common errors made by patients were device-independent errors and included not breathing out before actuation of the device (28.9%) and failure to breath-hold for a few seconds after inhalation (28.3%). These errors were observed in 40%-47% of patients. The number of patients making at least one error with breath-actuated inhalers was high; with less than 50% of patients inhaling correctly. Seventy-six per cent of patients made at least one error with pMDI compared to 49%-55% with breath-actuated inhalers. With respect to device-dependent errors, the pMDI fared worst with 69% of patients exhibiting at least one error, closely followed by the Turbuhaler (32%) and Autohaler (41%). Critical errors were made by only 11%-12% of patients treated with Aerolizer, Autohaler or Diskus compared to 28% and 32% of patients treated with pMDI and Turbuhaler, respectively. Over-estimation of good inhalation by GPs was maximal for Turbuhaler (24%) and lowest for Autohaler and pMDI (6%). Ninety per cent of GPs felt that participation in the study would improve error detection. Compliance may be improved by educating patients and physicians in the correct use of inhaler devices. Inhalers should be easy to use correctly, and have multiple feedback and control mechanisms which would reduce physician over-estimation of a correct inhalation, allow compliance to be monitored, facilitate patient self-education and give reassurance to patients in the real life setting.     

The rejuvenated pressurised metered dose inhaler

The pressurised metered-dose inhaler (pMDI) has now been available for 50 years. Once regarded as an inefficient and difficult-to-use device, the technology has evolved significantly over the last few years, particularly since the introduction of novel formulations containing hydrofluoroalkane (HFA) propellants. Many modern HFA pMDIs deposit drug more efficiently in the lungs, impact less forcefully on the back of the throat and feel less cold than their chlorofluorocarbon pMDI counterparts. An improved understanding of technical factors makes it possible to design HFA pMDIs to have specific spray properties, particularly in terms of fine particle dose and spray velocity. Device technology has also progressed with the introduction of compact and convenient breath-actuated, breath-coordinated and velocity-modifying devices, which help patients to achieve a reliable lung dose. Although it faces competition from dry powder inhalers and possibly from novel soft-mist inhalers containing liquid formulations, the rejuvenated HFA pMDI is a device with a significant future for asthma, chronic obstructive pulmonary disease and wider treatment indications.     

The rejuvenated pressurised metered dose inhaler

The pressurised metered-dose inhaler (pMDI) has now been available for 50 years. Once regarded as an inefficient and difficult-to-use device, the technology has evolved significantly over the last few years, particularly since the introduction of novel formulations containing hydrofluoroalkane (HFA) propellants. Many modern HFA pMDIs deposit drug more efficiently in the lungs, impact less forcefully on the back of the throat and feel less cold than their chlorofluorocarbon pMDI counterparts. An improved understanding of technical factors makes it possible to design HFA pMDIs to have specific spray properties, particularly in terms of fine particle dose and spray velocity. Device technology has also progressed with the introduction of compact and convenient breath-actuated, breath-coordinated and velocity-modifying devices, which help patients to achieve a reliable lung dose. Although it faces competition from dry powder inhalers and possibly from novel soft-mist inhalers containing liquid formulations, the rejuvenated HFA pMDI is a device with a significant future for asthma, chronic obstructive pulmonary disease and wider treatment indications.     

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 add-on devices for aerosol drug delivery: deposition studies and clinical aspects.

Add-on devices for pressurised metered dose inhalers (MDIs) improve "targeting" of drug to the lungs and can correct for hand-breath dyscoordination. Measurements of drug delivery from add-on devices by gamma scintigraphy have shown that compared to an MDI, oropharyngeal deposition is always reduced, and that lung deposition is generally either increased or unchanged. The total body dose may be reduced by over 80%. Increases in lung deposition may not result in improved bronchodilator response if the top of the dose-response curve has been reached. Add-on devices with one-way valves and mouthpiece or mask may enable asthma to be controlled with a smaller delivered dose of drug than from an MDI, and have proved to be viable lower cost alternatives to the use of nebulizers for delivering high dose bronchodilators to patients with severe acute asthma, and steroids to chronic asthmatics.     

Innovations and perspectives of metered dose inhalers in pulmonary drug delivery.

The phase-out of chlorofluorocarbons (CFCs) has spurred the development of alternative pulmonary drug delivery systems to pressurized metered dose inhalers (MDIs), such as dry powder inhalers and pocket size nebulizers. Reformulation of CFC-MDIs with hydrofluoroalkanes (HFAs) 134a and 227 is also an opportunity to improve these widely accepted systems with respect to ease of handling, compliance, dosing, and more reliable and efficient lung deposition. MDIs have the advantage to protect the drug substance from external parameters such as temperature and humidity and to meter and de-agglomerate the drug independent from patients inspiratory flow rates. Novel formulation technologies combined with improved valves and actuators should help to overcome dose uniformity and priming problems and will increase the percentage of fine particles capable of reaching the deeper regions of the lungs. Spacer mouthpieces can reduce the cold freon effect and undesired oropharyngeal deposition caused by the rapid evaporation of the propellant and plume velocity of the aerosol cloud. More advanced delivery devices may allow the patient to inhale at predetermined flow rates (fast/slow) to target the deposition of fine drug particles (1-6 microm) to specific sites into the lungs. Breath-actuated devices make these systems more effective and patient friendly. The above features in combination with numerical counters showing the remaining number of shots, and built-in blocking mechanisms to avoid tail-off dependent dose uniformity problems of the last labeled shots, should help to improve both acceptance and compliance of pMDIs compared to other inhalation devices. However, only those inhalation systems, which are accepted and appreciated by patients and offering an ambulatory treatment at reasonable cost, will be successful in a more and more competitive market. These issues must be considered in the development of future devices and formulations.     

A new method to evaluate plume characteristics of hydrofluoroalkane and chlorofluorocarbon metered dose inhalers

Two concerns raised when comparing metered dose inhalers (MDIs) to other inhalation devices are their relatively high throat deposition and the ‘cold-Freon’ effect seen in a small number of patients. The cold-Freon effect is presumed to be a result of the cold, forceful MDI plume impacting on the back of a patient’s throat. This in vitro study uses a new plume characterization method to determine the spray force and plume temperature of various MDIs. Spray force measurements were made for 28 marketed products consisting of bronchodilators, steroids, press-and-breathe, breath-actuated and nasal inhalers. Results show that chlorofluorocarbon (CFC)-containing MDIs produce extremely forceful and cold plumes. Several hydrofluoralkane (HFA)-containing MDIs produced much softer and warmer plumes, but two HFA products had spray forces similar to the CFC products. Although the type of propellant used can affect spray force, actuator orifice diameter is the most important factor. Data obtained from marketed products and experimental inhalers show that MDIs that have a low spray force also have low throat deposition.     

Advances in metered dose inhaler technology with the development of a chlorofluorocarbon-free drug delivery system.

The impending phaseout of chlorofluorocarbon (CFC)-containing metered dose inhalers (MDIs) has challenged the pharmaceutical industry to rethink and redesign many components of the technology involved in delivering asthma medication to the lungs. Along with the emergence of the first formulation using the nonozone-depleting propellant, hydrofluoroalkane (HFA) 134a to replace CFC propellants, advances in drug delivery technology have improved the performance characteristics of the MDI itself. Although MDIs have remained the mainstay of asthma therapy for 40 years, MDI technology still presents challenges. Some of the shortcomings of existing CFC MDIs affect the reliability of dosing. These challenges have been addressed in the development of the first CFC-free beta-agonist for the treatment of asthma. Airomir CFC-free (salbutamol sulfate; 3M Pharmaceuticals, St. Paul, MN), which is currently available in over 30 countries and was recently approved in the United States (Proventil HFA; Schering-Plough, Madison, NJ), incorporates numerous design and technological improvements which together with the introduction of CFC-free propellants mark the beginning of the next generation of asthma therapy. Although the new generation of CFC-free MDIs incorporates several improvements in dose reproducibility, these changes should be virtually transparent to the patient switching from a CFC MDI to a CFC-free MDI. What may be noticeable is a "softer puff," which is the result of valve and actuator redesign. The taste of the new CFC-free product may also be a little different yet totally acceptable to users.     

Nebulizer possibilities and limitations.

The ban of chlorofluorocarbon (CFC) propellants in metered dose inhalers (MDIs) gives rise to many alternatives and innovations: 1. CFC substitution by non-CFC propellants in MDIs. 2. battery driven miniaturized mechanical and piezoelectric nebulizers 3. revitalization of hand driven pocket nebulizers 4. self actuated dry powder inhalers (DPI's). All devices can be used with or without spacers. The choice for solid or liquid particles, e.g. powder or droplet aerosols, will also depend on the drug properties and the availability on the market for aerosol use. The nebulizer device will be chosen according to the medical need (emergency or long term treatment), the technical alternatives available in different countries, the possibility of patient cooperation (children, severely ill patients), and last not least marketing strategies and costs. The bronchial circulation is an important distribution system for medicine deposited by aerosol routes in the lung.     

Effect of an external resistance to airflow on the inspiratory flow curve

Inhalation is a convenient way to deliver drugs to the respiratory tract in the treatment of respiratory diseases. For dry powder inhalers (DPI's), the principle of operation is to use the patient-generated inspiratory flow as energy source for emptying of the dose system and the delivery of fine drug particles into the respiratory tract. Resistance to airflow of the inhaler device is a major determinant for the inspiratory flow profile through the dry powder inhaler that can be generated by the patient. Therefore, resistance to airflow is one of the design parameters for DPI's, that could be used to control the inspiratory flow profile, and is one of the parameters to optimise particle deposition in the airways. In this study the effect of resistance to airflow on different parameters of the inspiratory flow curves as generated by healthy subjects, asthmatics and COPD patients was determined. As a result of increased resistance to airflow, the peak inspiratory flow (PIF), the flow increase rate (FIR) and the inhaled volume to reach PIF is decreased. On the other hand, the total inhalation time as well as the 80% dwell time is increased. In general, tuning of the resistance to airflow in the design of a dry powder inhaler may improve the drug deposition in the respiratory tract.     

Novolizer: a multidose dry powder inhaler

Novolizer is a multidose breath-actuated dry powder inhaler (DPI) approved for use with salbutamol (albuterol) and budesonide. It has multiple patient feedback mechanisms and an inspiratory flow rate threshold designed to optimise dosage. In two studies, children aged 4-11 years with asthma correctly used Novolizer and generated mean peak inspiratory flow rates (PIFRs) through Novolizer of 76 and 92.7 L/min, well above the Novolizer threshold of 35-50 L/min. In healthy volunteers, median lung deposition of budesonide administered via Novolizer was 19.9-32.1% at mean PIFRs of 54-99 L/min. In a randomised, double-blind, single-dose study in patients with chronic obstructive pulmonary disease (COPD) and asthma, the 1-hour improvement from baseline in mean maximum forced expiratory volume in 1 second (FEV(1)) was 21.3% with inhalation of salbutamol through Novolizer, and 19.5% through Sultanol pressurised metered-dose inhaler (MDI). FEV(1) increased significantly in patients with asthma and COPD treated for 4 weeks in a randomised, open-label comparison of salbutamol through either Novolizer or Sultanol MDI. A randomised open-label study in adults with asthma treated with inhaled budesonide found equivalent improvements in FEV(1) and symptoms with Novolizer and Turbuhaler. Novolizer was well accepted overall. Most patients preferred it to previously used MDIs or DPIs. Only 4-5% found the taste feedback unacceptable. Physicians observed improved compliance over 4 weeks in 80% of patients with asthma using Novolizer.     

Transition to CFC-free metered dose inhalers--into the new millennium

Metered dose inhalers (MDIs) are the most popular vehicle for drug delivery into the lungs and some 500 million are manufactured each year. All MDIs marketed prior to 1995 contained chlorofluorocarbons (CFC) as a propellant. These are implicated in the depletion of stratospheric ozone and, except for specific exemptions, their production has been banned since 1996 under the terms of the Montreal Protocol. Hydrofluoroalkanes have been identified as suitable alternatives for MDI propellants but their physico-chemical properties differ significantly from CFCs and an extensive redevelopment and testing programme has been required to demonstrate the safety, quality and efficacy of HFA containing MDIs. Hydrofluoroalkanes contribute to global warming but the benefit to human health through continued MDI availability currently outweighs the environmental concern. Several HFA-MDIs have reached the market and the transition to replace existing CFC-MDIs is now underway.     

What plays a role in the choice of inhaler device for asthma therapy?

Inhalation is the preferred route of delivery for anti-asthma drugs. However, in reality inhalers are often prescribed on an empirical basis rather than on evidence-based awareness. Asthma management guidelines also guide inhaler choice, but they offer non-specific advice regarding inhaler choice, are very long and complicated and not conducive to rapid assimilation by a busy GP. In addition, device selection criteria differ according to who you are asking (i.e. the inhalation technologist, the physician or the patient). The ideal inhaler should be small and have a guided sequence of inhalation, leading patients in a logical sequence of events through the inhalation manoeuvre. It should be breath-activated, releasing medication only when all prerequisites for successful inhalation are met. Most importantly, there should be flow-independent deposition of drug in the lungs and feedback on the successfully performed inhalation manoeuvre to reassure the patient that the drug has been successfully released from the inhaler. The ideal inhaler should also have a low intrinsic airflow resistance, making it suitable for use by patients who have a low inspiratory airflow (e.g. children and elderly patients). In order to check for compliance, the ideal inhaler should have an accurate dose counter which is linked to correct inhalation rather than simply to dose release, and patients should be able to use an identical inhaler device to deliver each of their different medications. Finally, from an environmental and cost-effectiveness point of view, the ideal inhaler should be refillable. Among the currently available dry powder inhalers the Novolizer device fulfils several characteristics of an ideal inhaler for the treatment of asthma and chronic obstructive pulmonary disease (COPD).