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.     

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.     

Evidence of adequacy of the performance of the Pulvinal by measuring through-device peak inspiratory flow rate in severe airways obstruction in adults and children.

Pulvinal is a novel DPI designed to deliver inhaled drugs to the airways. Previous in vitro and in vivo data has suggested that the peak inspiratory flow rate (PIFR), measured through Pulvinal, does not depend on the severity of expiratory airflow obstruction and that the lowest PIFR values seem sufficient to deliver an effective bronchodilator dose. To study this further, we have investigated through-Pulvinal PIFR in categories of patients who are likly to generate low inspiratory flow rates. Three different patients' groups were selected (severe asthmatics, n = 52, including elderly) patients with severe chronic obstructive pulmonary disease (COPD, n = 21) and children with asthma (n = 16). This study aimed to measure the through-device PIFR and also to assess whether this correlated with measures of expiratory flow rate. Inspiratory flow measurements were made with a Pulvinal inhaler inserted into the adapted mouthpiece of a pneumotochograph. No significant correlations were seen between through-device PIFR and expiratory volumes or flow rates when expressed as percent predicted normal (forced expiratory volume in 1 sec [FEV1] and peak expiratory flow rate [PEFR]) in any of the three studied populations. A significant correlation was present for FEV1 (when expressed in liters) and through-device PIFR in the adult asthmatic and COPD study groups. In spite of the disease severity in adult populations and the age of children, the lowest generated PIFR values were within the range producing adequate performance of Pulvinal DPI (>20 L/min). We conclude that inspiratory flow rates generated through the Pulvinal inhaler can be adequate in asthma and COPD, including patients at the extremes of severity and age, who may theoretically have a limitation in their inspiratory flow.     

Key issues in inhalation therapy in children

In order to achieve asthma control it is essential that children receive the appropriate education and training pertaining to the management of their disease, are prescribed the correct medication according to severity, and most importantly, are prescribed the correct inhaler to ensure medication is deposited in their lungs. There are three major misconceptions which physicians and patients have regarding the use of inhalers in children. Firstly, that the nebulizer is more effective than a pressurised metered dose inhaler (pMDI) plus spacer in treating acute asthma in children. Secondly that using an inhaler correctly is easy, and lastly that correct use of the inhaler, once taught, persists over time. However, recent studies have shown that these conceptions are false. Firstly, comparable efficacy is achieved by treatment with inhaled corticosteroids or bronchodilators delivered through a nebulizer and a pMDI plus spacer, both when used to treat acute asthma and for maintenance therapy. Secondly, contrary to general opinion, using an inhaler correctly is difficult for children. Many children with asthma use their inhaler devices incorrectly, even after instruction for correct use of the inhaler. Thirdly, correct inhalation technique deteriorates over time; and inhalation instructions, therefore, should be given repeatedly to achieve and maintain correct inhalation technique in asthmatic children. The profile of the ideal inhaler comprises good drug deposition in the lower airways, deliverance of a consistent dose, being easy to teach and to use correctly, and being small in size and convenient to handle. It should also be multidose, require a low inspiratory airflow for activation, provide feedback to patients on correct use of the inhaler, be re-usable, have an appealing design and feel, and have a reliable dose counter which may help to monitor the patient's compliance. The Novolizer device, a new multidose dry powder inhaler (DPI), shows many of these characteristics making it potentially very suitable for children with asthma.     

NEXThaler,an innovative dry powder inhaler delivering an extrafine fixed combination of beclometasone and formoterol to treat large and small airways in asthma

Introduction: Airway inflammation and remodelling in asthma occur in the large airways and also in the small airways. The small airways are those < 2 mm in diameter and are significant sites of chronic asthmatic inflammation. It is important, therefore, to target the small as well as the large airways in any strategy for effective treatment of this disease.

Areas covered: The present review deals with the recently developed fixed dose drug combination of beclometasone dipropionate/formoterol fumarate that emits extrafine particles when delivered from an innovative dry powder inhaler (DPI), NEXThaler®. The aim is to present the technical and clinical aspects of aerosolized drug delivery to the lungs.

Expert opinion: The data show that the NEXThaler DPI is an efficient device for the management of persistent asthma. The evaluation of the inhalation profiles through the NEXThaler DPI demonstrates that device activation and consistent dose delivery occurs at patient achievable inhalation flow rates, and supports the broad utility of the NEXThaler DPI in patients with asthma. Overall, all the effectiveness, efficiency and satisfaction outcomes demonstrate the NEXThaler DPI is easy to use.     

Pharmacokinetics of budesonide and formoterol administered via 1 pressurized metered-dose inhaler in patients with asthma and COPD

In 3 open-label studies, the systemic bioavailability of budesonide and formoterol administered via pressurized metered-dose inhaler (pMDI) or dry powder inhaler (DPI) formulations was evaluated in asthma (24 children, 55 adults) or chronic obstructive pulmonary disease (COPD; n = 26) patients. Treatments were administered at doses high enough to estimate pharmacokinetic parameters reliably. Two of the studies included an experimental budesonide pMDI formulation. In study 1 (asthma, adults), budesonide area under the curve (AUC) was 32% and 31% lower and maximal budesonide concentration (C(max)) 45% and 56% lower after budesonide/formoterol pMDI and budesonide pMDI versus budesonide DPI. Formoterol AUC and C(max) were 13% and 39% lower after budesonide/formoterol pMDI versus formoterol DPI. In study 2 (asthma, children), budesonide AUC and C(max) were 27% and 41% lower after budesonide/formoterol pMDI versus budesonide DPI + formoterol DPI. In study 3 (COPD/asthma, adults), budesonide AUC and C(max) were similar and formoterol AUC and C(max) 18% and 22% greater after budesonide/formoterol pMDI versus budesonide pMDI + formoterol DPI (COPD). Budesonide and formoterol AUC were 12% and 15% higher in COPD versus asthma patients. In conclusion, systemic exposure generally is similar or lower with budesonide/formoterol pMDI versus combination therapy via separate DPIs or monotherapy and comparable between asthma and COPD patients.     

In Check Dial: accuracy for Diskus and Turbuhaler

OBJECTIVE: The In Check Dial was developed to evaluate whether a patient is able to generate an adequate peak inspiratory flow (PIF) through a certain inhalation device. The inhalation profile recorder (IPR) is a calibrated instrument that measures flows through Diskus and Turbuhaler in our research setting. The aim of this study was to compare the PIFs of patients when inhaling through a Diskus or Turbuhaler connected with the IPR (PIF_diskus and PIF_TH) to the flows through the corresponding orifices of the In Check Dial (Diskus_In Check and TH_In Check). METHODS: Twenty-four stable asthma and twenty-one chronic obstructive pulmonary disease (COPD) patients inhaled, on two separate occasions, in randomised order, via the Diskus or Turbuhaler connected with the IPR. Subsequently, patients inhaled through the In Check Dial using the orifices of Diskus or Turbuhaler. RESULTS: The difference between Diskus_In Check and PIF_diskus was 3.9 (11.9)l/min (P=0.038). The difference between TH_In Check and PIF_TH was 3.5 (10.6) l/min (NS). All Diskus- and Turbuhaler-inhalations were performed with the minimum required flow of 30 l/min. However, four COPD patients inhaled with the non-optimal flow (<60 l/min) through the Turbuhaler. The In Check Dial did not indicate two of them. CONCLUSION: Measuring PIF through Diskus and Turbuhaler using the IPR and the In Check Dial, respectively shows a disagreement of 3.9l/min. A disagreement of 3.5l/min was found for the Turbuhaler. The In Check Dial did not identify two of four patients as 'non-optimal' users.     

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.     

Recent advances in aerosol therapy for children with asthma.

Inhalational drug delivery is the primary mode of asthma therapy in children and is the main focus of this article. Pressurized metered dose inhalers (pMDIs) are now the method of choice in infants and children under 5 years old, when used in combination with an appropriate valved holding chamber or spacer. Spacers are particularly important for steroid inhalation to maximize lung deposition and minimize unwanted oropharyngeal deposition. Optimal inhalation technique with a pMDI-spacer in infants is to inhale the drug by breathing tidally through the spacer. Drug delivery to the lungs using pMDIs can vary greatly, depending on the formulation used and the age of the child. Dry powder inhalers (DPIs) are driven by the peak inspiratory flow of the patient and are usually not appropriate for children under 5 or 6 years of age. Nebulizers continue to play a role in the treatment of acute asthma where high doses of bronchodilator are required, though multiple doses via pMDI spacer may suffice. Important drug delivery issues specific to children include compliance, use of mask versus mouthpiece, lower tidal volumes and inspiratory flows, determination of appropriate dosages, and minimization of adverse local and systemic effects.     

Active and intelligent inhaler device development

The dry powder inhaler, which has traditionally relied on the patient's inspiratory force to deaggregate and deliver the active agent to the target region of the lung, has been a successful delivery device for the provision of locally active agents for the treatment of conditions such as asthma and chronic obstructive pulmonary disease (COPD). However, such devices can suffer from poor delivery characteristics and/or poor reproducibility. More recently, drugs for systemic delivery and more high value compounds have been put into DPI devices. Regulatory, dosing, manufacturing and economic concerns have demanded that a more efficient and reproducible performance is achieved by these devices. Recently strategies have been put in place to produce a more efficient DPI device/formulation combination. Using one novel device as an example the paper will examine which features are important in such a device and some of the strategies required to implement these features. All of these technological advances are invisible, and may be irrelevant, to the patient. However, their inability to use an inhaler device properly has significant implications for their therapy. Use of active device mechanisms, which reduce the dependence on patient inspiratory flow, and sensible industrial design, which give the patient the right clues to use, are important determinants of performance here.     

Inspiratory flow rates through a novel dry powder inhaler (Clickhaler) in pediatric patients with asthma.

Inspiratory flow profiles through a novel dry powder inhaler (DPI) (Clickhaler; Innovata Biomed Ltd, St. Albans, UK) were recorded in 17 pediatric patients (aged 7-16 years) with stable mild to moderate asthma. Most patients (n = 14) could generate high peak inspiratory flows (PIFs) (> 60 L/min) and high flows early in the flow profile. These flows have been shown to be adequate to deaggregate and deliver micronized drug with this delivery system.     

儿童哮喘472例吸入疗法技术及辅助吸药装置使用分析

目的分析不同年龄儿童哮喘患者对吸入疗法技术及辅助吸药装置的正确使用情况,旨在指导临床医师正确选择吸入药物、吸药装置以及如何指导病儿正确使用。方法对我院2004年2月至2008年7月哮喘专科门诊病儿使用吸入药物及吸入装置情况进行观察、指导、随访,分为吸药前有哮喘专科医师指导吸药组和无专科医师指导组。结果吸药前选择正确的吸药装置有哮喘专科医师指导吸药组和无专科医师指导组吸药错误率分别为25.54%、88.52%.经X~3检验P<0.05,差别具有显著性意义,经哮喘专科医师指导吸药后,于用药1周、1个月随访观察,两组吸药错误率分别为16.84%、18.33%,6.79%、9.81%,经X~2检验P>0.05,差别无显著性意义。吸药前选择正确的吸药装置有哮喘专科医师指导吸药组与直接用压力定量气雾剂吸药组比较:虽经哮喘专科医师指导吸药,并于1周、1个月随访观察纠正,但直接用压力定量气雾剂吸药组吸药错误率在用药当时、1周、1个月分别为88.38%、79.06%、67.44%,两组比较经÷~2检验,P<0.05差别具有显著性意义。无专科医师指导组:采取有活瓣的带面罩的储雾罐吸入压力定量气雾剂常见错误依次为:储雾罐的口鼻罩仅叩住患儿的口,未罩住患儿的鼻占22%;用药前未振荡气雾剂占18%;压力定量气霉剂未朝上占15.6%;空气压泵霉化吸入溶液常见错误依次为:用空气压泵面罩仅叩住患儿的口未叩住患儿的鼻占16%;使用吸入激素,吸药后未洗脸漱口占12%;未定期清洁储雾罐占9%;准纳器常见错误依次为:将准纳器吸嘴放入口中,不知道用力吸气以保证吸入药物占14%;吸药后屏气时间未达10s以上,或口唇屏气但鼻腔呼气占11%。直接用压力定量气雾剂常见错误依次为:不能在深吸气的同时按下阀门占66%,用药前未振荡气雾剂占16%;吸入激素吸药后未漱口占12%。结论根据患者年龄正确选择吸入药物及装置;使用吸入药物前由哮喘专科医师正确指导,井定期随访纠正错误是保证吸入技术正确及疗效的关键。     

Inhaler Use in Hospitalized Patients with Chronic Obstructive Pulmonary Disease or Asthma: Assessment of Wasted Doses

Background:

Hospitalized patients with chronic obstructive pulmonary disease (COPD) or asthma routinely have inhaled medications ordered for acute and maintenance therapy. Treatment may be administered via metered-dose inhaler (MDI) or dry-powder inhaler (DPI). These products must be appropriately labeled to be released home with the patient or discarded before discharge.

Objective:

To assess the amount and estimated cost of wasted doses of medications via MDI or DPI for hospitalized patients with COPD/asthma.

Methods:

A retrospective study was conducted at a university-affiliated hospital. Patients admitted between January 2011 and June 2012 with a primary diagnosis of COPD or COPD with asthma and who were ≥40 years of age were included. Information collected included use of albuterol, ipratropium, inhaled corticosteroids, long-acting beta agonist, or tiotropium and whether treatments were given by nebulizer, MDI, MDI plus valved holding chamber (VHC), or DPI. The number of doses dispensed, as well as doses not used, via MDI, MDI + VHC, or DPI were collected from electronic medical records. Costs associated with wasted medications were evaluated.

Results:

Of 555 patient admissions screened, 478 (mean age, 66 years; 58% women; 74% African American) met study criteria. Of the total MDI or DPI doses dispensed, 87% were wasted, and associated hospital cost was approximately $86,973.

Conclusions:

Substantial waste of inhaled medications was found in our study. Practical strategies are needed to reduce wasted inhalers. Further assessment of this problem is needed in other US hospitals.     

Use of inhaler devices in pediatric asthma

Inhalation is the preferred route for asthma therapy, since it offers a rapid onset of drug action, requires smaller doses, and reduces systemic effects compared with other routes of administration. Unfortunately, inhalation devices are frequently used in an empirical manner rather than on evidence-based awareness.A wide variety of nebulizers are available. Conventional jet nebulizers are highly inefficient, as much of the aerosol is wasted during exhalation. However, incorporating an extra open vent into the system has considerably increased the amount of drug that patients receive. Breath-assisted open vent nebulizers limit the loss of aerosol during exhalation, but are dependent on the patient's inspiratory flow. Ultrasonic nebulizers produce a high mass output and have a short nebulization time, but are inefficient for delivering suspensions or viscous solutions. Adaptive aerosol delivery devices release a precise dose that is tailored to the individual patient's breathing pattern. Nebulizers have several drawbacks, and their use should be limited to patients who cannot correctly manage other devices.Pressurized metered-dose inhalers (pMDI) are practical, cheap and multidose. However, there are several problems with their use. Breath-actuated MDI are easy to use and can be activated by very low flow. However, young children may not be able to use them efficiently. Dry powder inhalers (DPI) are portable and easy to use. They are indicated either for rescue bronchodilator therapy or for regular treatment with inhaled corticosteroids and long-acting bronchodilators. The use of spacers reduces oropharyngeal deposition and improves drug delivery to the lung. Spacers do not require patient coordination, but some general rules must be followed for their optimal use.Thus, the choice of a delivery device mainly depends on the age of the patient, the drug to be administered and the condition to be treated. Proper education is also essential when prescribing an inhalation device.     

Inhalation profiles in asthmatics and COPD patients: reproducibility and effect of instruction.

Turbuhaler and Salbutamol-Diskus produce therapeutic doses at peak inspiratory flow (PIF) of >30 L/min. However, the optimum flow for Fluticasone-Diskus and Turbuhaler, in terms of total emitted dose and fine particle mass, is >60 L/min. The Turbuhaler achieved a higher output at this flow, as compared to Diskus. For pMDI 25 < PIF < 90 L/min, an actuation time of 0.0-0.2 sec is optimal. The aim of this study was to examine the incidence of optimum inhalation profiles, the effect of instruction, reproducibility, and the relationship between inhalation profiles and patient characteristics in stable asthmatics and mild/moderate/severe COPD patients. For each device, triplicate inhalation profiles were recorded during 6 sessions in a 10-week period. All patients achieved PIF > 30 L/min using Diskus. After instruction, all Diskus inhalations were performed with >60 L/min, except 7% of the inhalations of the severe COPD patients. At least 95% of the Turbuhaler inhalations was also performed with the minimum flow; however, 19% of the inhalations of the severe COPD patients were not optimally performed. The hand-lung coordination was inadequate in 40% of pMDI inhalation profiles, and 80% was performed with a too high flow. The reproducibility of PIF of both dry powder inhalers (DPIs) was very high (coefficient of variation = 4-10%). The reproducibility of the pMDI variables was lower (coefficient of variation = 9-18%). The major lung function variables predictive for PIF(diskus) and PIF(turbuhaler) were maximal inspiratory mouth pressure (MIP), PIF, and inspiratory capacity. No significant predictive lung function variables for PIF(pMDI) were found. Most patients performed reproducible optimum inhalation profiles through Diskus and Turbuhaler. However, in the severe COPD group, 7-19% of the patients were not able to generate the optimum flows through the DPIs. For these patients, a flow-independent aerosol delivery system might be more suitable. The majority of patients were using the pMDI incorrectly. Instruction had no effect. So, we concluded that the pMDI should not be used in these patient groups because of the coordination problems.     

儿童哮喘吸入治疗及最大呼气峰速值测定的临床评价

目的 观察吸入疗法治疗儿童哮喘的疗效。方法 对72例哮喘儿童使用倍氯米松长期吸入,沙丁胺醇间断吸入,峰流速 仪监测肺功能,跟踪观察6-12个月。结果 72例患中,显效50例,有效21例,无效1例,总有效率98.61%。急诊就诊率由治疗前95.83%降到治疗后22.22%,急诊住院率由治疗前45.83%降到治疗后1.39%。最大呼气峰速值（PEFR）在治疗12个月后较治疗6个月及治疗前明显增加。治疗期间未发现不良反应。结论 吸入疗法治疗儿童哮喘疗效可靠、方法简单,无副作用,简易呼气峰速 仪对哮喘儿童监测具有实用价值。     

Improving outcomes in elderly patients with asthma

Although often regarded as a disease of childhood, asthma is common in elderly people. Although recent figures show a decline over the past few years in the number of asthma deaths in children and younger adults, the same is not true of older adults, in whom most asthma deaths occur. Differences between asthma in young and old patients are seen not only in response to treatment. The nonspecific presentation of asthma in elderly adults means that the diagnosis of asthma is difficult to make. In addition, research suggests that physicians are reluctant to use spirometry and measurement of reversibility when investigating respiratory symptoms in old people. This leads to a tendency to label breathless or wheezy elderly patients as having chronic obstructive pulmonary disease (COPD) rather than asthma. In turn, patients with a diagnosis of COPD are less likely to be treated with bronchodilators and corticosteroids. Treatment guidelines for the management of asthma in children and younger adults may need to be adapted when applied to older patients. Reduced perception of bronchoconstriction may lead to underuse of bronchodilators prescribed 'as required'. The bronchodilator response to beta2-agonists is attenuated as part of the normal aging process, and other groups of bronchodilator medications should be considered. Inhaler technique can be a particular problem in elderly patients with asthma, requiring careful choice of inhaler device. However, the frequent presence of multiple pathology and multiple medication in this age group enhances the risk of adverse effects from oral preparations, and so the inhaled route should be preferred wherever possible. Underestimation of the severity of an acute exacerbation of asthma by both patient and doctor has been suggested as a contributory factor to poor outcome in older people. Since the cardiovascular responses to hypoxia and bronchoconstriction tend to diminish with increasing age, objective measures of asthma severity (peak flow monitoring and blood gas estimation) are essential in this age group.     

Ventolin Diskus and Inspyril Turbuhaler: an in vitro comparison.

Dose delivery (total emitted dose, or TED) from dry powder inhalers (DPIs), pulmonary deposition, and the biological effects depend on drug formulation and device and patient characteristics. The aim of this study was to measure, in vitro, the relationship between parameters of inhalation profiles recorded from patients, the TED and fine particle mass (FPM) of Diskus and Turbuhaler inhalers. Inhalation profiles (IPs) of 25 patients, a representative sample of a wide range of 1500 IPs generated by 10 stable asthmatics, 3 x 16 (mild/moderate/severe) COPD patients and 15 hospitalized patients with an exacerbation asthma or COPD, were selected for each device. These 25 IPs were input IPs for the Electronic Lung (a computerdriven inhalation simulator) to determine particle size distribution from Ventolin Diskus and Inspyril Turbuhaler. The TED and FPM of Diskus and FPM of Turbuhaler were affected by the peak inspiratory flow (PIF) and not by slope of the pressure-time curve, inhaled volume and inhalation time. This flow-dependency was more marked at lower flows (PIF < 40 L/min). Both the TED and FPM of Diskus were significantly higher as compared to those of the Turbuhaler [mean (SD) TED(_diskus) (%label claim) 83.5 (13.9) vs. TED(_turbuhaler) (72.5 (11.1) (p = 0.004), FPM(_diskus) (%label claim) 36.8 (9.8) vs FPM(_turbuhaler) (28.7 (7.7) (p < 0.05)]. The TED and FPM of Diskus and FPM of Turbuhaler were affected by PIF, the flow-dependency being greater at PIF values below 40 L/min. Lower PIFs occurred more often when using Turbuhaler than Diskus, since Turbuhaler have a higher resistivity, requires substantially higher pressure in order to generate the same flow as Diskus. TED, dose consistency and the FPM were higher for Diskus as compared to Turbuhaler. The flow dependency of TED and FPM was substantially influenced by inhalation profiles when not only profiles of the usual outpatient population were included but also the real outliers from exacerbated patients.     

Dose emission and aerodynamic characterization of the terbutaline sulphate dose emitted from a Turbuhaler at low inhalation flow

Previously, dose emission below 30?L min^?1 through DPI has not been routinely determined. However, during routine use some patients do not achieve 30?L min^?1 inhalation flows. Hence, the aim of the present study was to determine dose emission characteristics for low inhalation flows from terbutaline sulphate Turbuhaler.

Total emitted dose (TED), fine particle dose (FPD) and mass median aerodynamic diameter (MMAD) of terbutaline sulphate Turbuhaler were determined using inhalation flows of 10–60?L min^?1 and inhaled volume of 4?L.

TED and FPD increase significantly with the increase of inhalation flows (p <0.05). Flows had more pronounced effect on FPD than TED, thus, faster inhalation increases respirable amount more than it increases emitted dose. MMAD increases with decrease of inhalation flow until flow of 20L min^?1 then it decreases.

In vitro flow dependent dose emission has been demonstrated previously for Turbuhaler for flow rates above 30?L min^?1 but is more pronounced below this flow. Minimal FPD below 30?L min^?1 suggests that during routine use at this flow rate most of emitted dose will impact in mouth. Flow dependent dose emission results suggest that Pharmacopoeias should consider the use variety of inhalation flows rather than one that is equivalent to pressure drop of 4 KPa.     

Drug Delivery in Pediatric Patients with Asthma

This review discusses published evidence on the use of metered dose inhaler (MDI)/spacer combinations and nebulizers for delivering β₂ adrenoeeptor agonists (β₂ agonists) in stable and acute severe childhood asthma. Although nebulizers have been the mainstay of inhalation therapy in childhood asthma for many years, these devices are cumbersome, bulky, time-consuming, and expensive to use. As a result, over the past decade the emphasis of inhalation therapy in children has shifted from nebulizers to metered-dose inhalers (MDI) in combination with spacer devices. MDI/spacer combinations have been shown to be a practical and effective way of delivering medications for inhalation in children with asthma, irrespective of their age. Lung deposition increases with age, being low in young children. This underscores the need for administering relatively high nominal dosages of medication when using an MDI/spacer in young children; the most practical approach is to use the same dose, irrespective of the child’s age or weight. In children with both stable chronic asthma and acute severe asthma, numerous studies have shown that β₂ agonists can be delivered by MDI/spacer at least as effectively and safely as by nebulizer. Although nebulizers may still play a role in status asthmaticus (because they allow combined administration of β₂ agonists, anticho-linergic agents, and oxygen in a single procedure), the vast majority of children of all ages with acute severe asthma can be managed effectively and safely by β₂ agonists delivered via MDI/spacer. This cost-effective and practical approach should, therefore, be preferred.