A dry powder inhaler with reduced mouth-throat deposition.

A novel, compact, and highly efficient dry powder inhaler (DPI) with low mouth-throat deposition is described. The performance of this DPI was evaluated by measuring both (1) the total aerosol deposition in and distal to an idealized mouth-throat cast and (2) the fine particle fraction (FPF) using a standard Mark II Anderson impactor. Ultraviolet (UV) spectroscopy techniques were used in the aerosol deposition measurements. Two inhalation aerosol powders, namely budesonide (extracted from a Pulmicort/Turbuhaler multi-dose device, 200 microg/dose) and ciprofloxacin + lipid + lactose (in-house), were dispersed by the DPI at a steady inhalation flow rate of 60 L/min. The newly developed DPI had a total aerosol delivery distal to the mouth-throat cast of 50.5% +/- 3.04% and 69.7% +/- 1.5% for the budesonide and ciprofloxacin + lipid + lactose aerosols, respectively. This is a significant improvement over the Turbuhaler original device delivery of 34.5% +/- 5.2%, particularly considering that in vitro mouth-throat deposition dropped from 27.5% +/- 5.4% with the budesonide Turbuhaler to 11.0% +/- 3.5% with the present inhaler. The different lung deliveries from the same inhaler for the two formulations above also confirm that the overall performance of an inhaler is optimizable via powder formulations.     

Design and application of a new modular adapter for laser diffraction characterization of inhalation aerosols

An inhaler adapter has been designed for the characterization of the aerosol clouds from medical aerosol generators such as nebulizers, dry powder inhalers (dpis) and metered dose inhalers (mdis) with laser diffraction technology. The adapter has a pre-separator, for separation of large particles (i.e. carrier crystals) from the aerosol cloud before it is exposed to the laser beam. It also has a fine particle collector for measuring the emitted mass fraction of fines by chemical detection methods after laser diffraction sizing. The closed system enables flow control through the aerosol generators and all test conditions, including ambient temperature and relative humidity, are automatically recorded. Counter flows minimize particle deposition onto the two windows for the laser beam, which make successive measurements without cleaning of these windows possible. The adapter has successfully been tested for nebulizers, mdis and dpis. In a comparative study with ten nebulizers it was found that these devices differ considerably in droplet size (distribution) of the aerosol cloud for the same 10% aqueous tobramycin solution (volume median diameters ranging from 1.25 to 3.25 microm) when they are used under the conditions recommended by the manufacturers. The droplet size distribution generated by the Sidestream (with PortaNeb compressor) is very constant during nebulization until dry running of the device. Comparative testing of dpis containing spherical pellet type of formulations for the drug (e.g. the AstraZeneca Turbuhaler) with the adapter is fast and simple. But also formulations containing larger carrier material could successfully be measured. Disintegration efficiency of a test inhaler with carrier retainment (acting as a pre-separator) could be measured quite accurately both for a colistin sulfate formulation with 16.7% of a lactose fraction 106-150 microm and for a budesonide formulation with a carrier mixture of Pharmatose 325 and 150 M. Therefore, it is concluded that, with this special adapter, laser diffraction may be a valuable tool for comparative inhaler evaluation, device development, powder formulation and quality control. Compared to cascade impactor analysis, laser diffraction is much faster. In addition to that, more detailed and also different information about the aerosol cloud is obtained.     

Patient perception and acceptability of multidose dry powder inhalers: a randomized crossover comparison of Diskus/Accuhaler with Turbuhaler.

This study was designed to provide information on correct use and preference to features and device handling of two multidose dry powder inhalers, the Diskus/Accuhaler and the Turbuhaler. A total of 169 powder-naive patients (mean age 40 years) with asthma or chronic obstructive pulmonary disease (COPD) were enrolled in a randomized crossover comparison of both inhalers. An effective use of either inhaler was assessed before (leaflet only) and after inhaler education. Ease of use especially during an attack and the presence of a dose counter were regarded as the most important features for an ideal inhaler. The percentage of correct handling maneuvers and the percentage of patients achieving 100% of correct maneuvers increased significantly (p < 0.001) after inhaler education in both devices, but percentage of correct use after the intervention was significantly higher for the Diskus/Accuhaler (92.6%) than for the Turbuhaler (89.8%; p = 0.036). Overall 60% of patients thought the Diskus/Accuhaler was preferable to the Turbuhaler (p < 0.001). The main reasons given were presence of a dose counter, perceived ease of use including ease of learning to use, design, and attached cover. Among those who preferred the Turbuhaler device, the main reason cited was small size, discreetness, and ease of holding. In the multivariate analysis, inhaler education (p = 0.005) and education level (p = 0.009) were significantly associated with the percentage of correct maneuvers. Age, sex, or tested inhaler showed no effect on appropriateness of the inhalation technique.     

A critical comparison of the dose delivery characteristics of four alternative inhalation devices delivering salbutamol: pressurized metered dose inhaler, Diskus inhaler, Diskhaler inhaler, and Turbuhaler inhaler.

Salbutamol is a short-acting beta 2 agonist which is effective as a rescue therapy in the treatment of asthma. This study uses in vitro test methods to compare the capability of four alternative devices to deliver an accurate and precise dose of salbutamol. It is demonstrated that the conventional metered dose inhaler (MDI) achieves excellent accuracy and precision in dose delivery. Additionally, it is the most efficient inhaler in terms of generating in-vitro a fine particle fraction from the dose. A spacer device has been shown to further enhance the dosing characteristics. When tested over a wide range of inspiratory air flow rates, the Diskus (GlaxoWellcome, Hertfordshire, UK) has comparable accuracy and precision to the MDI tested at 60 L/min, and it offers an advantage over two alternative dry powder inhalers (DPIs), delivering a more consistent dose across the range of flow rates tested and being more efficient at generating a fine particle fraction than either Turbuhaler (Astra, Lund, Sweden) or Diskhaler (GlaxoWellcome) at both 28 and 60 L/min inspiratory flow rates. Diskus, Diskhaler, Ventolin, Volumatic, and Rotadisk are trademarks of the GlaxoWellcome Group of companies. The Accuhaler is the alternative to the Diskus in those countries where the Diskus trademark is not available. Inspiryl and Turbuhaler are trademarks of the Astra Group of companies.     

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.     

Comparison of In Vitro Deposition of Pharmaceutical Aerosols in an Idealized Child Throat with In Vivo Deposition in the Upper Respiratory Tract of Children

Purpose

Deposition of drug emitted from two commercially available inhalers was measured in an in vitro child oral airway model and compared to existing in vivo data to examine the ability of the child model to replicate in vivo deposition.

Methods

In vitro deposition of drug from a QVAR® pressurized metered dose inhaler (pMDI) and Pulmicort® Turbuhaler® dry powder inhaler (DPI) in an Idealized Child Throat (1) and downstream filter was measured using UV spectroscopy and simulated realistic breathing profiles. Potential effects of ambient relative humidity ranging from 10% to 90% on deposition were also considered.

Results

In vitro QVAR pMDI deposition in the idealized mouth-throat at 50% RH (39.2?±?2.3% of delivered dose) compared well (p?>?0.05) with in vivo extrathoracic deposition in asthmatic children age 8 to 14 (45.8?±?12.3%). In vitro Turbuhaler DPI deposition in the idealized mouth-throat at 50% RH (69.0?±?1.5%) matched in vivo extrathoracic deposition (p?>?0.05) in 6 to 16 year old children with cystic fibrosis (70.4?±?21.2%). The effects of ambient humidity were found to be insignificant for Turbuhaler and minor for QVAR.

Conclusions

The Idealized Child Throat successfully mimics in vivo deposition data in school age children for the inhalers tested, and may provide a standard platform for optimizing pediatric treatment with inhaled pharmaceutical aerosols.     

A new Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) to evaluate pulmonary drug absorption for metered dose dry powder formulations

Absorption studies with aerosol formulation delivered by metered dose inhalers across cell- and tissue-based in vitro models of the pulmonary epithelia are not trivial due to the complexity of the processes involved: (i) aerosol generation and deposition, (ii) drug release from the carrier, and (iii) absorption across the epithelial air-blood barrier. In contrast to the intestinal mucosa, pulmonary epithelia are only covered by a thin film of lining fluid. Submersed cell culture systems would not allow to studying the deposition of aerosol particles and their effects on this delicate epithelial tissue.We developed a new Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) to mimic the inhalation of a single metered aerosol dose and its subsequent deposition on filter-grown pulmonary epithelial cell monolayers exposed to an air-liquid interface. The reproducibility of deposition of these dry powder aerosols and subsequent drug transport across Calu-3 monolayers with commercially available dry powder inhalers containing salbutamol sulphate or budesonide could be demonstrated.In the context of developing new dry powder aerosol formulations, PADDOCC appears as a useful tool, allowing reducing animal testing and faster translation into clinical trials.     

Deposition of corticosteroid aerosol in the human lung by Respimat Soft Mist inhaler compared to deposition by metered dose inhaler or by Turbuhaler dry powder inhaler.

Fourteen mild-to-moderate asthmatic patients completed a randomized four-way crossover scintigraphic study to determine the lung deposition of 200 microg budesonide inhaled from a Respimat Soft Mist Inhaler (Respimat SMI), 200 microg budesonide inhaled from a Turbuhaler dry powder inhaler (Turbuhaler DPI, used with fast and slow peak inhaled flow rates), and 250 microg beclomethasone dipropionate inhaled from a pressurized metered dose inhaler (Becloforte pMDI). Mean (range) whole lung deposition of drug from the Respimat SMI (51.6 [46-57]% of the metered dose) was significantly (p < 0.001) greater than that from the Turbuhaler DPI used with both fast and slow inhaled flow rates (28.5 [24-33]% and 17.8 [14-22]%, respectively) or from the Becloforte pMDI (8.9 [6-12]%). The deposition pattern within the lungs was more peripheral for Respimat SMI than for Turbuhaler DPI. The results of this study showed that Respimat SMI deposited corticosteroid more efficiently in the lungs than either of two widely used inhaler devices, Turbuhaler DPI or Becloforte pMDI.     

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.     

Comparative lung delivery of salbutamol given via Turbuhaler and Diskus dry powder inhaler devices

Objective: The environmental concerns surrounding the use of chlorofluorocarbons (CFC) have led to a resurgence of interest in dry powder inhaler devices. The aim of our study was to compare two commonly used dry powder inhaler devices, namely the Turbuhaler and Diskus. Methods: Eight healthy volunteers with a mean (SEM) age of 21 years (0.8) were studied using a randomised single-investigator blind crossover design. Single doses of 1.2 mg salbutamol as Turbuhaler (12 × 100 μg) and Diskus (6 × 200 μg) were administered over 6 min. Mouth rinsing was performed after every inhalation. Lung delivery from each device was assessed by measuring the early plasma salbutamol profile at 5, 10, 15 and 20 min after inhalation. Results: Significant differences in lung delivery were found between the Diskus and the Turbuhaler for salbutamol C_max 3.21 vs 4.04 ng · ml⁻¹, respectively and C_av 2.65 vs 3.73 ng · ml⁻¹, respectively. This amounted to a 1.28-fold difference (95% CI 1.09 to 1.45) between these devices for C_max and a 1.42-fold difference (95% CI 1.57 to 1.66) for C_av. Conclusion: We have demonstrated that, in vivo, the Turbuhaler dry powder inhaler produces significantly greater lung delivery of salbutamol than the Diskus. This illustrates that dry powder inhaler devices may have different in vivo deposition characteristics. Received: 27 January 1997 / Accepted in revised form: 21 May 1997     

驱动器的规格与吸入辅助装置对气雾剂体外沉积性质的影响

目的 考察驱动器的规格——孔径、孔长以及吸入辅助装置的使用对气雾剂体外沉积性质的影响.方法 以自制丙酸氟替卡松混悬型气雾剂为模型药物,装配不同规格的驱动器,使用Andersen多级撞击器(Andersen cascade impactor,ACI)测定体外沉积率;将丙酸氟替卡松气雾剂装配筛选好的特定规格的驱动器,分别在不使用吸入辅助装置与使用吸入辅助装置的情况下,对体外沉积性质进行对比研究.结果 在孔径固定的情况下,随着孔长的延长,驱动器的残留量降低,Andersen多级撞击器装置的L型连接管沉积量增加,微细粒子剂量降低.在孔长固定的情况下,随着孔径的增加,驱动器的残留量降低,Andersen多级撞击器装置的L型连接管沉积量增加,微细粒子剂量降低.根据试验结果、混悬型气雾剂本身的剂型特点以及驱动器的实际使用情况,最终,将0.42 mm孔径、0.70 mm孔长的驱动器作为优选驱动器;在使用吸入辅助装置的情况下,Andersen多级撞击器装置L型连接管的沉积量极大地降低,微细粒子剂量增加,原来沉积在L型连接管的大粒子很大一部分被截留在吸入辅助装置当中.结论 驱动器的规格会对吸入气雾剂的体外沉积产生一定的影响,在药品研发的过程中,可根据气雾剂产品的具体特点(溶液型或混悬型,原料药的粒径大小等)进行驱动器的筛选;吸入辅助装置的使用可以提高气雾剂的药物利用率,推荐患者用药时使用.     

Studies of the human oropharyngeal airspaces using magnetic resonance imaging IV--the oropharyngeal retention effect for four inhalation delivery systems.

Magnetic resonance imaging (MRI) of the oropharyngeal region from 20 adult volunteers using four model inhalation devices (varying mouthpiece diameters, airflow resistances) and tidal breathing was carried out. Statistical analysis (convex hull method) selected 12 scans from 80 data sets representing the extremes of all dimensions in the population. Twelve physical mouth-throat models were made by stereolithography using the exact scan data. The aim was to produce models with varying dimensions to span the adult population, and to investigate if oropharyngeal dimensions affected throat retention for different delivery systems. In an in vitro analysis, the models were used to determine the retention effect of the oropharyngeal airspaces when drug aerosols were administered from four inhalation delivery systems: a pressurised metered dose inhaler (pMDI), two different dry powder inhalers (DPIs A and B), and a nebulizer. The aims of this work were to determine the key parameters governing mouth-throat retention and whether retention was dependent on the delivery system used. Characterizing the throat models by measuring 51 different dimensional variables enabled determination of the most influential variables for dose retention for each inhalation delivery system. Throat model retention was found to be dependent on the delivery system (pMDI approximately DPI(A) > DPI(B) > Neb.). The most influential variable was the total throat model volume. Throat models representing high, median, and low oropharyngeal filtration in healthy adults have been identified.     

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.     

Emitted dose estimates from Seretide Diskus and Symbicort Turbuhaler following inhalation by severe asthmatics

The dose emitted from dry powder inhalers may be inhalation flow-dependent. Using an ex vivo method, the Electronic Lung, we have measured the aerodynamic characteristics of the emitted dose for both active constituents from Seretide Diskus (salmeterol xinafoate 50 mcg; fluticasone propionate 500 mcg) and Symbicort Turbuhaler (formoterol 6 mcg; budesonide 200 mcg). Electronic inhalation profiles were collected from 20 severe asthmatics (mean PEFR 53% predicted) when they inhaled using a placebo Seretide Diskus and a placebo Symbicort Turbuhaler. These were replayed in the Electronic Lung with the respective active inhaler in situ. Mean(S.D.) peak inhalation flow rates (PIFR) through the Diskus and Turbuhaler were 94.7(32.9) and 76.8(26.2) l min(-1), respectively. From the Electronic Lung the Diskus inhalation profiles provided a mean(S.D.) fine particle dose (FPD) for fluticasone propionate and salmeterol of 20.4(4.8) and 18.4(4.4)% labelled dose. For Turbuhaler inhalation profiles the FPD was 23.1(12.9) and 20.7(11.1)% labelled dose for budesonide and formoterol, respectively. The linear (p < 0.001) relationships between FPD against PIFR for budesonide and formoterol were 3 (p = 0.002) and 2.8 (p = 0.007) times steeper than fluticasone propionate and salmeterol, respectively. The results highlight a more significant effect of inspiratory flow on variable dosage emission when using the Symbicort Turbuhaler compared with the Seretide Diskus.     

Airmax: a multi-dose dry powder inhaler

Airmax is a multi-dose dry powder inhaler. An internal pump measures out the drug dose using controlled air pressure. Inhalation transports the drug into a cyclone separator (where active drug is separated from the lactose carrier) and then into the patient airway. In vitro studies indicate that Airmax may be less dependent on airflow than Turbuhaler for drug delivery; greater dose consistency was seen with administration of budesonide via Airmax than via Turbuhaler. At a low flow rate, the lung deposition of budesonide administered via Airmax was greater than that of budesonide administered via Turbuhaler or a pressurised metered dose inhaler in patients with asthma. In cumulative-dose studies, the mean forced expiratory volume in 1 second (FEV(1)) achieved with salbutamol (albuterol) or formoterol administered via Airmax was equivalent to that achieved with twice the dose administered via dry powder inhalers. black triangle In randomised, double-blind studies, budesonide administration via Airmax was equivalent to administration via Turbuhaler with regards to FEV(1) and improvement in asthma symptoms in both adults and children with asthma. The concentration of adenosine monophosphate producing a 20% fall in FEV(1) increased from pretreatment levels by a greater extent with budesonide administered via Airmax, compared with Turbuhaler. Both adults and children preferred Airmax to Turbuhaler, and more found Airmax easier to use. In one study, the majority of children found learning how to use Airmax trade mark easier than learning how to use Turbuhaler.     

Resistivities of placebo and active Diskus inhalers compared

OBJECTIVE: Verbal instruction and demonstration of inhalation technique are essential to enhance the effectiveness of inhalation therapy. Placebo devices are commonly used to instruct patients. It is not obvious that patients, who inhale with an adequate flow through an empty placebo Diskus, would also be able to do so with active inhalers containing a strip with powder. The presence of powder may result in a change in resistivity. We compared the resistivities of a placebo Diskus being empty; a powder filled Diskus inhaler and a Diskus inhaler with an empty blister. METHODS: A Diskus inhaler was placed in a box, which enabled measurement of pressure drop and flow rates. Ten placebo and ten Ventolin Diskus inhalers were measured. Twelve pressure- and flow-profiles were recorded through each device. After each simulated inhalation through a powder filled blister, a second inhalation was performed through the empty blister. The resistivity was calculated by pressure-flow equation. RESULTS: The resistivity of the empty placebo Diskus inhaler was slightly but significantly higher than both blister filled inhalers, with or without powder (0.0215 vs. 0.0211 and 0.0211 (kPa)(0.5) (l min(-1))(-1)) (P<0.001). CONCLUSION: Patients who are capable of generating sufficient flow through a placebo Diskus will surely be capable of generating equivalent flows through a Diskus inhaler containing a strip with active drug substance.     

Drug delivery from the Turbuhaler and Nebuhaler pressurized metered dose inhaler to various age groups of children with asthma.

A total of 198 children aged 3 to 15 years inhaled a single dose of 200 micrograms budesonide from a Nebuhaler pressurized metered dose inhaler (pMDI) and a Turbuhaler dry powder inhaler in a randomized crossover study. The budesonide dose delivered to a patient was assessed by measuring the amount of drug deposited on a filter inserted between the inhaler outlet and the patient's mouth. The dose of budesonide deposited on the filter and the estimated dose of particles with a mass median aerodynamic diameter (MMAD) of 5 microns or less after inhalation from the Turbuhaler were both approximately twice the values inhaled from the pMDI Nebuhaler in children less than 5 years of age (P < 0.01). The variation in the dose delivered to the patient was similar for the two inhalers in children over 5 years old. In 3- to 4-year-old children, dose delivery to the patient was higher and/or more consistent from the pMDI Nebuhaler than from the Turbuhaler. Filter dose after Turbuhaler treatment varied significantly from peak inspiratory flow rate through the Turbuhaler (PIFTbh) (P < 0.01). The percentage of children producing a PIFTbh greater than 50 L/min decreased with age (89%, 45%, and 14% in 5-, 4-, and 3-year-old children, respectively). It is concluded that drug delivery to a child with asthma varies with age and inhalation device. Further studies are needed to assess the clinical importance of this finding.     

Assessment of handling of inhaler devices in real life: an observational study in 3811 patients in primary care.

The correct use of inhalation devices is an inclusion criterion for all studies comparing inhaled treatments. In real life, however, patients may make many errors with their usual inhalation device, which may negate the benefits observed in clinical trials. Our study was undertaken to compare inhalation device handling in real life. A total of 3811 patients treated for at least 1 month with an inhalation device (Aerolizer, Autohaler, Diskus, pressurized metered dose inhaler (pMDI), or Turbuhaler) were included in this observational study performed in primary care in France between February 1st and July 14th, 2002. General practitioners had to assess patient handling of their usual inhaler device with the help of a checklist established for each inhaler model, from the package leaflet. Seventy-six percent of patients made at least one error with pMDI compared to 49-55% with breath-actuated inhalers. Errors compromising treatment efficacy were made by 11-12% of patients treated with Aerolizer, Autohaler, or Diskus compared to 28% and 32% of patients treated with pMDI and Turbuhaler, respectively. Overestimation of good inhalation by general practitioners was maximal for Turbuhaler (24%), and lowest for Autohaler and pMDI (6%). Ninety percent of general practitioners felt that participation in the study would improve error detection. These results suggest that there are differences in the handling of inhaler devices in real life in primary care that are not taken into account in controlled studies. There is a need for continued education of prescribers and users in the proper use of these devices to improve treatment efficacy.     

In vivo-in vitro comparison of deposition in three mouth-throat models with Qvar and Turbuhaler inhalers.

In vitro polydisperse aerosol deposition in three mouth-throat models, namely, the USP (United States Pharmacopeia) mouth-throat (induction port), idealized mouth-throat, and highly idealized mouth-throat, was investigated experimentally. Aerosol particles emitted from two commercial inhalers, Qvar (pMDI) and Turbuhaler (DPI), were used. The in vitro deposition results in these three mouth-throat models were compared with in vivo data available from the literature. For the DPI, mouth-throat deposition was 57.3 +/- 4.5% for the USP mouth-throat, 67.8 +/- 2.2% for the idealized mouth-throat, and 69.3 +/- 1.1% for the highly idealized mouth-throat, which are all relatively close to the in vivo value of 65.8 +/- 10.1%. In contrast, for the pMDI, aerosol deposition in the idealized mouth-throat (25.8 +/- 4.2%) and the highly idealized mouth-throat (24.9 +/- 2.8%) agrees with the in vivo data (29.0 +/- 18.0%) reported in the literature better than that for the USP mouth-throat (12.2 +/- 2.7%). In both cases, the USP mouth-throat gives the lowest deposition among the three mouth-throat models studied. In summary, both the idealized mouth-throat and highly idealized mouth-throat improve the accuracy of predicted mean in vivo deposition in the mouth-throat region. This result hints at the potential applicability of either the idealized mouth-throat or highly idealized mouth-throat as a future USP mouth-throat standard to provide mean value prediction of in vivo mouth-throat deposition.     

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.