Influence of temperature on the emitted dose of an oral metered dose inhaler

The performance of metered dose inhalers is critical for the efficient delivery of drugs to the intended site of deposition in the respiratory tract. The temperature at which metered dose inhaler products are used by patients may influence the physicochemical characteristics of the emitted dose. Product performance characteristics of a metered dose inhaler containing beclomethasone dipropionate and oleic acid in a blend of chlorofluorocarbon propellants, Freon-11 and Freon-12, were determined by cascade impaction analysis and dose delivery through the valve after the metering chamber was loaded and actuated at 4 degrees C, 23 degrees C, and 40 degrees C. The dose delivered from the valve was not affected by the temperature at which the metering chamber was loaded and actuated. The mass median aerodynamic particle size of the emitted aerosol decreased and the percentage respirable fraction increased as the temperature was increased. The geometric standard deviation of the particle size distribution was not significantly affected by the temperature at which the metering chamber was loaded and actuated. The temperature at which a metered dose inhaler is used by a patient may influence the amount of drug that is potentially respirable; therefore, the dose expected to be delivered and the corresponding therapeutic effect may also be affected.     

Automatic actuation of a dry powder inhaler into a nonelectrostatic spacer

This article describes a new "automatic spacer" device, which has been developed to improve the delivery of inhaled medication to young children. In the device, a dry powder inhaler (DPI) is mechanically actuated into a nonelectrostatic spacer, producing an aerosol cloud of fine drug particles (aerodynamic diameter, < 4.7 microm) with a long half-life. The new device combines the principal advantages of the conventional spacer and the DPI. It has the potential to provide a high ratio between lung dose and pharyngeal dose, without need for coordination or forced inhalation, and it avoids exposure of the patient to the additives and propellants used in pressurized metered dose inhalers. Studies with the prototype device show a high yield of fine drug particles in the aerosol (mass median aerodynamic diameter, 2.8 microm), a high repeatability of drug delivery owing to the mechanical nature of the actuation (relative standard deviation, 12%), and a prolonged residence time of the fine particle aerosol (half-life of the fallout of the fine particles, 82 s). These features should prove advantageous in the treatment of young children with inhaled medication.     

HIV-1 gp120-dependent induction of apoptosis in antigen-specific human T cell clones is characterized by ''tissue'' transglutaminase expression and prevented by cyclosporin A

Inhalation is the method of choice for delivering therapeutic agents to the lung. The advent of metered-dose inhalers (MDIs) has made inhalation easier, less expensive and more efficient. However, 20-50% of patients are unable to use MDIs correctly. The main problems are: 1) impact of aerosol particles in the mouth (responsible for side-effects); 2) poor co-ordination between firing the MDI and breathing; 3) and too fast an inspiration. Various spacer devices have been designed to overcome these problems. These are: large volume devices, which reduce the oral impact and select the respirable particles; devices equipped with a one-way valve that reduces co-ordination problems; indication of too rapid an inspiration by a high-flow mark. The introduction of these devices has resulted in an improved bronchial/oral deposition rate and a reduced incidence of side-effects. Training and education of patients is fundamental in ensuring the correct use of inhalers.     

Formoterol inhaled as dry powder or via pressurized metered-dose inhaler in a cumulative dose-response study

Formoterol administered by a dry-powder (DP) capsule inhaler was compared with a pressurized metered-dose inhaler (pMDI) with regard to bronchodilating and systemic effects. The study used a double-blind, crossover, double-dummy technique. Twelve patients with moderate reversible asthma in a stable phase were examined on two separate study days, and the inhalers were given in randomized order. After baseline measurements, increasing doses of formoterol were given at intervals of 75 min. FEV1 and heart rate and tremor measurements were repeated after each dose, and the doses were 12 + 12 + 24 + 48 micrograms, giving a total dose of 96 micrograms. The peak expiratory flow rate (PEFR) was recorded in the morning before the first dose, after the last dose, and then repeatedly at home until 19 h after the last dose. There was an equal increase in ventilatory capacity at each dose level, independent of inhaler device. Repeated PEFR measurements after the last dose did not reveal any differences in duration of effect. There was a slight but statistically significant increase in heart rate and tremor after the highest doses of the DP formulation compared to the pMDI. These systemic effects can probably be explained by the reduced oral deposition of the aerosol caused by using a spacer. This study indicates that the DP and pMDI formulations of formoterol are equipotent in bronchodilation.     

Randomised crossover trial of salbutamol aerosol delivered by metered dose inhaler, jet nebuliser, and ultrasonic nebuliser in chronic lung disease

AIMS: To compare the efficacy of salbutamol delivered by metered dose inhaler (MDI), jet nebuliser, and ultrasonic nebuliser in ventilated infants with chronic lung disease. METHODS: Twenty preterm ventilated infants with chronic lung disease were enrolled in two studies. In study 1 (n = 10), each infant was given 200 micrograms of salbutamol at 4 hour intervals and in random sequence from a metered dose inhaler-spacer device, a jet nebuliser, and an ultrasonic nebuliser with a small medication cup. The infants were monitored for heart rate, transcutaneous pO2, pCO2, and oxygen saturation, respiratory system resistance and compliance before and after each treatment. Infants in study 2 (n = 10) were similarly studied except for the use of a different jet nebuliser. RESULTS: The mean (SEM) maximum percentage decreases in respiratory system resistance, observed at 30 minutes after aerosol delivery were study 1: MDI: 44.3 (4.3)%; jet: 32.3 (3.4)%; ultrasonic: 56.1 (3.2)%; study 2: MDI: 28.6 (1.0)%; jet: 16.9 (1.4)%; ultrasonic: 42.1 (1.6)%. During the first hour after treatment, a significantly faster heart rate and higher transcutaneous pO2 were associated with the use of the ultrasonic nebuliser or MDI than with the jet nebulisers in both studies. The use of the ultrasonic nebuliser but not the other devices also resulted in a lower transcutaneous pCO2 and improved respiratory system compliance in study 2. CONCLUSIONS: These findings suggest that among the devices tested, the delivery of salbutamol aerosol to the lower respiratory tract was greatest using the ultrasonic nebuliser, and least with the jet nebulisers.     

Multiple actuations of salbutamol MDI into a spacer device reduce the amount of drug recovered in the respirable range

We wanted to determine the amount of salbutamol available in respirable particles from the Volumatic spacer device after one, two or five actuations of a metered-dose inhaler into the spacer prior to analysis. A glass multistage liquid impinger was used to determine particle size. Aerosol was sampled after one, two or five actuations from a metered-dose inhaler into a Volumatic spacer. Each experiment was repeated four times. The amount of salbutamol recovered per actuation in particles less than 5 microns (mean and 95% confidence intervals) was: 54.3 micrograms (48.3-60.1) after one actuation; 42.4 micrograms (38.2-46.5) after two actuations, and 20.7 micrograms (17.5-23.9) after five actuations. We conclude that multiple actuations of salbutamol into the Volumatic spacer do not linearly increase the amount of drug available for inhalation. To maximize drug delivery, single actuations should be used prior to inhalation. In comparative studies of drugs and dosages, it must be remembered that the amount of drug delivered is not the same as that administered.     

Assessment of patient acceptance and inhalation technique of a pressurized aerosol inhaler and two breath-actuated devices

OBJECTIVE: To assess inhalation technique in patients after written instruction alone, written and verbal instruction, and clinical use of two new inhalation devices. DESIGN: Randomized, crossover evaluation of the albuterol Diskhaler and the terbutaline Turbuhaler. SETTING: Canadian tertiary-care hospital. PATIENTS: Twenty hospitalized adults with asthma or chronic obstructive pulmonary disease currently using an albuterol metered-dose inhaler (MDI). Nineteen patients received Diskhaler, 16 received Turbuhaler, 15 received both inhalers, and 10 patients used both inhalers for three days each. INTERVENTIONS: Patients were randomized to receive either Diskhaler or Turbuhaler for three days. Inhaler technique was assessed after written instruction, written plus verbal instruction, at the first scheduled dose after instruction, and after three days of clinical use. Patients remaining in the hospital after three days crossed over to the other study inhaler and the same protocol was followed. MAIN OUTCOME MEASURES: Patient inhalation technique was assessed and compared for the MDI, Diskhaler, and Turbuhaler. RESULTS: Assessment of MDI technique revealed that 35 percent of patients used their MDI correctly on the first puff, and 42 percent used it correctly on the second puff. Following written instruction alone, correct technique was demonstrated by 32 percent of patients with Diskhaler and 6 percent with Turbuhaler. Technique significantly improved following verbal instruction, although 40 percent of the patients required up to three attempts to demonstrate correct technique on at least one of the study inhalers. After three days of clinical use, correct technique was demonstrated in only 54 percent of the Diskhaler and 64 percent of the Turbuhaler assessments. Performance at this assessment was, however, significantly better on the Turbuhaler than on the MDI (p = 0.01). Performance on the Diskhaler was not significantly different from the performance on the other inhalers. CONCLUSIONS: Written instruction alone is inadequate in teaching correct inhalation technique. Verbal instruction and technique assessment are essential for patients to achieve proper technique. Patients may perform better on the Turbuhaler than on other inhalation devices.     

Differential immunological aberrations in patients with primary and secondary Sj?gren''s syndrome

PURPOSE: To evaluate the dependence of fine particle dose charge (FPD charge) generated from powder inhalers on physico-chemical properties of the inhalation powder, inhaler type, deaggregation mechanism, dose number and/or retained powder. METHODS: Electrostatic charges were determined on micronized powders and aerosolized fine particle doses withdrawn from two, high efficiency, multidose powder inhalers, Turbohaler and prototype Dryhaler. The behavior of terbutaline sulfate, budesonide, albuterol (sulfate and base), beclomethasone dipropionate and lactose was assessed before and after aerosolization. RESULTS: Both inhalers conferred triboelectric FPD charges during aerosolization in the range -400 pC through +200 pC. Specific charges (charge/unit mass) on the fine particle doses of budesonide from Dryhaler were significantly less than those from Turbohaler (p < 0.01). Electrostatic charges on the potentially respirable cloud of terbutaline sulfate generated by Bricanyl Turbohaler were positive and/or negative and unpredictable. With Pulmicort Turbohaler, FPD charges on budesonide were always positive. Dryhaler was used to determine the chemical dependence of fine particle triboelectrification during the aerosolization of pure materials. A triboelectric series was constructed from the Dryhaler results ranking the powders from positive to negative as budesonide > lactose > albuterol sulfate > terbutaline sulfate > or = albuterol > or = beclomethasone dipropionate. CONCLUSIONS: While there was no evidence of FPD charge dependence upon dose number with either inhaler, FPD charges were dependent upon the powder under investigation, as well as the construction and deaggregation mechanism of the inhaler. The specific charge on the fine particle dose of budesonide from Turbohaler corresponded to approximately 200 electronic charges per particle, a value which is known to affect both total and regional aerosol deposition in the human lung. Electrostatic charge effects may be important determinants of aerosol behavior and should not be neglected.     

An EPR dosimetry method for rapid scanning of children following a radiation accident using deciduous teeth

The purpose of this study was to investigate the formulation and delivery of a protein in a pressurized metered-dose inhaler (pMDI) containing HFA 134a as the propellant for aerosol delivery. Ethanol and surfactants, including polyoxyethylene 10 oleyl ether (Brij 97), polyoxyethylene 20 oleyl ether (Brij 98), polyoxyethylene sorbitan monooleate (Tween 80) and Aerosol OT (AOT), were investigated as formulation adjuvants to improve the dose delivery characteristics of the model protein (bovine serum albumin) containing pMDI formulations. The aqueous solution of a surfactant and protein was lyophilized to obtain a solid carrier system of the protein. Readily dispersible suspensions were obtained by suspending this solid carrier system in HFA 134a with ethanol as a dispersing aid. The formulations containing Tween 80 resulted in the highest respirable fraction. This study suggested a potential formulation containing a lyophilized complex of surfactant and protein readily dispersible in HFA 134a for delivering a therapeutic protein to the respiratory tract by inhalation.     

Inhalation of single vs multiple metered-dose bronchodilator actuations from reservoir devices. An in vitro study

Differences in inhalation technique with reservoir or spacer devices may affect metered-dose inhaler (MDI) dose availability to a patient. PURPOSE: This study examined the effect of single vs multiple actuations of an MDI into reservoir devices on dose delivery of albuterol, with three clinically available reservoir brands. METHODS: An in vitro lung model simulated inspiration from the MDI reservoir system. Albuterol (Proventil; Schering) was delivered by MDI, with the Monaghan Aerochamber, the Diemolding Healthcare Division (DHD) aerosol cloud enhancer (ACE), and the Schering InspirEase, using standardized volumes and inspiratory flows of 30 L min(-1). The MDI was actuated into each brand of reservoir 1, 2, or 3 times in rapid succession, followed by a single inhalation. Aerosol dose at the reservoir mouthpiece was captured on a cotton filter, dissolved in ethanol, and measured with a spectrophotometer at 278 nm. RESULTS: For all three brands of reservoir, less accumulated dose of drug is delivered with multiple actuations than with multiple single actuations each followed by inhalation. The total dose in milligrams increased significantly with two multiple actuations compared with one actuation in the Aerochamber and ACE (p<0.01), but not in the InspirEase (p>0.05). The Aerochamber, ACE, and InspirEase delivered a mean total dose (SD) of 0.0264 mg (0.012), 0.0271 mg (0.007), and 0.0136 mg (0.006), respectively, with one actuation compared to 0.0485 mg (0.011), 0.0453 mg (0.013), and 0.0218 mg (0.009) with two multiple actuations. The increase in total dose with three multiple actuations was not significant compared to two actuations for any of the brands tested (p>0.05). Although total dose increased with multiple actuations, a decline in efficiency was seen with two and three multiple actuations, compared to single actuation. The dose delivered per actuation decreased for the Aerochamber, ACE, and InspirEase from 0.0264 mg (0.012), 0.0271 mg (0.007), and 0.0136 mg (0.006) with one actuation, to 0.0243 mg (0.006), 0.0226 mg (0.006), and 0.0109 mg (0.005), respectively, with two multiple actuations, for losses of 8.0%, 16.6%, and 19.9% in dose per actuation for each brand. A further decline in delivery per actuation to 0.0164 mg (0.001), 0.0184 mg (0.004), and 0.0097 mg (0.005) for the 3 brands, respectively, was found with 3 multiple actuations before inhalation. This was a loss of 37.9%, 32.1%, and 28.7% of the dose per single actuation in each brand. There was no significant difference between the Aerochamber and the ACE in dose availability with 1, 2, or 3 actuations, but both of these brands provided significantly more drug than the InspirEase. CONCLUSION: Maximal aerosol bronchodilator from an MDI reservoir was given by single actuations each followed by a breath. Two rapid actuations followed by a breath will give a significant accumulation of dose with some loss when compared to two single actuations each followed by inhalation. Three multiple actuations led to a loss of approximately one third of the drug dose obtainable with three single actuations each followed by inhalation, for all three brands.     

A mentor-based laboratory management elective for residents

BACKGROUND: A combination metered-dose inhaler aerosol containing ipratropium bromide and albuterol sulfate has been reported to be more effective than either of its components in patients with chronic obstructive pulmonary disease. The dose of albuterol sulfate is equal in moles per liter to the dose of albuterol base used in the commercially available metered-dose inhalers. OBJECTIVE: To compare the safety and efficacy of the combination of ipratropium bromide and albuterol sulfate with a commonly prescribed albuterol metered-dose inhaler containing albuterol base alone. METHODS: Investigators at different sites performed a double-blind, 29-day trial involving 357 patients with chronic obstructive pulmonary disease. Efficacy measurements were taken at 15, 30, and 60 minutes after treatment with study medication and then hourly up to 6 hours on days 1 and 29 of the trial. The primary end point was improvement in forced expiratory volume in 1 second. Clinical status was followed up and safety monitoring was also performed. RESULTS: The combination produced a significantly greater peak and mean improvement in forced expiratory volume in 1 second over albuterol base alone on both test days. Similar changes were seen with forced vital capacity. Evaluations of clinical status were better for patients receiving combination therapy, and some improvements were statistically significant. The overall incidence of adverse effects was similar in the 2 treatment groups. CONCLUSION: We conclude that a combination of ipratropium bromide and albuterol sulfate is more effective at improving pulmonary function than albuterol base alone, with no potentiation of adverse effects.     

Inhaler therapy for adults with obstructive lung diseases: powder or aerosol?

When prescribing inhalation medication in the ambulant treatment of patients with asthma and chronic obstructive pulmonary disease (COPD), a choice can be made between dry powder inhaler (DPI) and pressurized metered dose inhalers (pMDI). The degree of deposition in the lower airways depends on the dose delivery via the inhaler and the mean diameter of the released particles (MMAD). With a DPI, dose delivery and MMAD depend on the inspiratory flow rate. With a pMDI dose delivery and MMAD do not depend on the inspiratory flow rate but on hand-mouth co-ordination. The main determinants for the choice of a DPI or a pMDI are the degree of co-operation and co-ordination, and the inspiratory flow rate of the patient.     

Nebulisation of surfactants in an animal model of neonatal respiratory distress

AIMS: To evaluate pulmonary deposition and gas exchange following nebulisation of two surfactants by either a jet or an ultrasonic nebuliser. METHOD: After bronchoalveolar lavage (BAL), 19 rabbits were ventilated in four groups. Group A1 (n = 5) and A2 (n = 6) received Technetium-99m labelled Exosurf, and groups B1 (n = 4) and B2 (n = 4) received radiolabelled Survanta. Groups A1 and B1 received jet nebuliser therapy, whereas groups A2 and B2 received ultrasonic nebuliser. Pulmonary deposition, distribution, and blood gases were determined. RESULTS: Pulmonary deposition as per cent of initial dose and mg lipid) was 0.28(0.10)% or 0.59(0.21) mg in group A1, 1.05(0.23)% or 2.21(0.48) mg in group A2, 0.08(0.02)% or 0.30(0.08) mg in group B1, and 0.09(0.02)% or 0.34(0.08) mg in group B2. Deposition in group A2 was greater than in other groups (p = 0.001). Group A2 showed a small improvement in blood gases. CONCLUSIONS: Even the highest deposition--ultrasonic nebuliser with Exosurf--achieved limited clinical effect. The aerosol route is currently not effective for surfactant treatment.     

The problems of radon therapy: its benefits and risks]

Local administration of drugs by means of aerosol device is widely used in the treatment of asthma. Nevertheless, the effectiveness of this method depends on an adequate inhalation technique (IT), which available evidence has shown to be rather problematic. The aim of this study was to assess IT in out-patients with bronchial asthma who frequently use aerosol therapy with Pressurized Metered dose inhalers (MDI), pressurized inhalers with spacer (MDI-S) and the Astra-Draco Turbuhaler system (TH). A sample of 150 adults with asthma were evaluated. These patients had been followed up for than two years and they often used one of the devices mentioned above. The IT has broken down into several steps for each procedure. Percentages of patients with one error in the IT were 50%, 44% and 42% for MDI, MDI-S and TH procedures, respectively. 18%, 20% and 14% of patients committed three errors in the IT, respectively. Differences detected were not significant. Seven patients committed errors in every step of the IT. In conclusion, the level of errors found in our study is high, similar to that cited in the existing literature. It is also roughly equivalent for the three devices tested. We believe that the proper teaching monitoring of IT skills is highly important in the treatment of bronchial asthma.     

Patient satisfaction with the Diskhaler and the Diskus inhaler, a new multidose power delivery system for the treatment of asthma

To evaluate patient satisfaction with two breath-actuated powder inhalers (Diskhaler and Diskus), investigators asked patients to complete questionnaires as part of a randomized, double-masked, double-dummy, placebo-controlled study of fluticasone propionate powder (500 mg twice daily) in the treatment of chronic persistent asthma. At baseline, patients rated the importance of various inhaler attributes (i.e., ease of use, ease of loading with medication, ease of holding and operating, ease of cleaning, and ease of telling how many doses of medication are left). After 2 weeks of placebo and 6 and 12 weeks of active therapy, patients rated the inhalers on these same attributes. They also rated their general satisfaction with the inhalers and how comfortable they were using them. After 12 weeks, patients also rated the durability and convenience of carrying each device and were asked to indicate which they preferred. Data were available from 213 patients. All seven inhaler attributes measured were considered important by the majority of patients (71% to 91%), contributing to the validity of the patient-rated performance assessments. After 12 weeks of use, 57% to 88% of patients expressed a high level of satisfaction with the performance of the Diskhaler on all attributes; a high level of overall satisfaction (72%) and comfort (79%) was reported with this inhaler. Patients rated the performance of the Diskus inhaler very favorably, with 76% to 96% expressing a high level of satisfaction on all attributes; a high level of overall satisfaction (87%) and comfort (85%) was reported with this inhaler. At end point, 61.4% preferred the Diskus inhaler, 25.4% preferred the Diskhaler inhaler, and 13.2% expressed no preference. These breath-actuated powder inhalers may be acceptable alternatives to traditional metered-dose inhalers for the treatment of patients with asthma.     

Coagulatory response after femoral instrumentation after severe trauma in sheep

Budesonide inhalation powder, available as Pulmicort Turbuhaler, is a corticosteroid with a high ratio of local to systemic effects that is administered to treat persistent asthma. The Turbuhaler achieves lung deposition approximately twice that of a metered-dose inhaler (MDI) with or without a spacer device. Budesonide inhalation powder has clinical efficacy equivalent to that of fluticasone and beclomethasone, but it has lower systemic bioavailability and fewer systemic side effects. As with other inhaled corticosteroids, dysphonia and oral candidiasis are the most frequent adverse effects, and systemic effects are infrequent. The initial starting dosage is 200 microg (1 puff) twice/day and may be increased to 800 microg twice/day in adults or 400 microg twice/day in children. Patients prefer the Turbuhaler to the MDI, Diskhaler, and Rotahaler because it is easier to use and more convenient to carry.     

Characterization by isotope method of the performance of the pneumatic nebulizer NL9 Atomizer in the production of colistin, tobramycin and amiloride aerosols

The objective of this study was to assess the performance of a new pneumatic nebuliser NL9 Atomisor. The performance was assessed in terms of particle distribution, fraction nebulised, fraction inhaled and percentage of particles of a diameter of between 1 and 4 microns for the nebulisation of physiological serum, colistin, tobramycin and amiloride. The solutions were nebulised in the approved formula for their reconstitution as used in the clinic after the addition of sodium pertechnetate. The validity of this indirect isotopic method has been shown before. The nebuliser was coupled, during the nebulisation, to a pump respirator with six settings. The fraction nebulised was defined as the percentage of the volume of the solution which had left the aerosol generator at the end of the nebulisation. The fraction inhaled was defined as a percentage of the volume of the solution which was gathered at the end of the nebulisation on a filter placed in the inspiratory circuit of the aerosol generator. The study of the distribution of aerosol particle sizes was carried out using a cascade impactor at ten stages. Each of these parameters was determined in triplicate for the four solutions studied. The nebulised fraction consisted of between 33.5 and 58.6% (mean 49.7 +/- 8.1%). The inhaled fraction consisted of between 14 and 30.4% (mean 24.5 +/- 5.5) and the duration of nebulisation was between 10 and 20 minutes. The MMAD was between 1.6 microns with tobramycin 3.5 microns with physiological serum.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cervical ripening

Electrostatic charge in plastic spacer devices has been shown in vitro to reduce delivery of asthma medications intended for inhalation, but the effect of static charge on in vivo drug deposition is unknown. A six-way randomized crossover study was conducted in 10 mild asthmatic patients. Two plastic spacers (Nebuhaler and Volumatic) and one metal spacer (Nebuchamber) were tested. The spacers were used either "primed" or "unprimed". Priming was performed by firing 20 doses of placebo aerosol into a new spacer, hence coating the inner surface with surfactant and minimizing static charge. Unprimed spacers were new and were not treated. Pressurized aerosol canisters delivering budesonide (200 microg Pulmicort) were radiolabelled with the radionuclide 99mTc and lung deposition was measured by gamma scintigraphy. The radiolabel was shown to be a valid marker for the drug substance prior to the clinical phase of the study. Priming significantly increased mean whole lung deposition following inhalation from plastic spacers (Nebuhaler primed 37.7% and unprimed 26.7%, p=0.01; Volumatic primed 32.0% and unprimed 22.1%, p=0.02). Priming had no effect on the mean whole lung deposition following inhalation from the Nebuchamber (primed 33.5% and unprimed 32.9%). Lung deposition in vivo from plastic spacer devices will vary according to the electrostatic charge on the spacer walls. Priming reduces retention of drug on plastic spacer devices and increases lung deposition. Metal spacers are not susceptible to static charge, which should result in more predictable lung deposition.     

Urinary bacteriology in the elderly in the tropical zone: results of 5 years of activities at the CHU of Fann in Dakar

The distribution pattern of budesonide in the nasal passages and lungs was investigated in 10 healthy subjects after nasal inhalation. The subjects inhaled drug powder, radiolabelled with 99mTc, at maximum flow rate (46.3 +/- 6.8 l/min) and at 29.9 +/- 2.5 l/min via Turbuhaler. At both flows, the majority of the dose was deposited in the anterior part of the nasal cavity on a single, rather localized area, but some particles also penetrated more posteriorly into the main nasal passages and to the lungs. At maximum flow rate the nasal deposition was 65.2% (range 39.5-84.1%) and the lung deposition 4.7% (range 1.4-9.3%) of the metered dose, and at 30 l/min, the nasal deposition was 67.6% (range 49.7-81.6%) and the lung deposition was 4.2% (range 1.7-7.9%). A large fraction of the metered dose was deposited in the nasal adaptor of the inhaler during the administration (mean values 29 and 28%, for the two inhalation flows). Of the dose actually reaching the subject, 91 and 93% (mean values) was deposited in the nose. There were no statistically significant differences in distribution pattern between the two inhalation flows.     

Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines: comparison of RESPIMAT with conventional metered-dose inhalers with and without spacer devices

STUDY OBJECTIVES: To compare lung deposition of fenoterol or flunisolide administered from a novel, multidose inhalation device delivering liquid droplets (RESPIMAT; Boehringer Ingelheim Ltd; Bracknell, UK) or from conventional metered-dose inhalers (MDIs) with and without spacers. DESIGN: Two randomized, three-way crossover studies. SETTING: Clinical research laboratory. PARTICIPANTS: Healthy, nonsmoking volunteers. INTERVENTIONS: In one study, radiolabeled aerosols of fenoterol from the RESPIMAT device and from a conventional MDI with or without an Aerochamber spacer (Trudell Medical; London, Ontario Canada). In the second study, radiolabeled aerosols of flunisolide from a RESPIMAT device, from a RESPIMAT device modified by inclusion of a baffle/impactor in the mouthpiece, and from a conventional MDI with an Inhacort spacer (Boehringer Ingelheim; Ingelheim, Germany). MEASUREMENTS AND RESULTS: Assessment of the deposition of fenoterol or flunisolide in the lung and oropharynx using gamma scintigraphy. Safety was assessed based on reported adverse effects and spirometry (FEV1, FVC, and peak expiratory flow rate) to detect any paradoxical bronchoconstriction. The RESPIMAT device delivered significantly more fenoterol to the lungs than either an MDI alone or an MDI with Aerochamber (39.2% vs 11.0% and 9.9% of metered dose, respectively; p<0.01). Oropharyngeal deposition of fenoterol from the new device was lower than that from the MDI (37.1% vs 71.7%, respectively; p<0.01). The RESPIMAT device deposited significantly more flunisolide in the lungs compared with MDI plus spacer (44.6% vs 26.4%, respectively; p<0.01), while resulting in similar oropharyngeal deposition (26.2% vs 31.2%, respectively). Introduction of a baffle into the RESPIMAT system reduced lung deposition of flunisolide to 29.5%, and oropharyngeal deposition to 7.8% (p<0.01). CONCLUSION: The RESPIMAT device may prove to be an effective alternative to MDIs for the administration of inhaled bronchodilators and corticosteroids. The high lung deposition and low oropharyngeal deposition may lead to improved efficacy and tolerability of inhaled medications, especially corticosteroids.