Salbutamol Metered-dose Inhaler Research Articles

Metered-dose inhalers. II. Particle size measurement variation

Three apparatuses, the Andersen Cascade Impactor (ACI), the Marple-Miller Impactor (MMI) and the Twin Impinger (TI) were compared in the measurement of particle size distribution (PSD) of four commercially available salbutamol metered-dose inhalers (MDIs). The ACI was fitted with two induction ports. One was that currently described in the United States Pharmacopeia (USP) and the second had a larger volume. Parameters calculated included Mass Median Aerodynamic Diameter (MMAD), Geometric Standard Deviation (GSD) and Fine Particle Dose (FPD). The results demonstrated that several of these parameters were device-dependent and that all of the apparatuses were able to detect differences between some of the MDIs. The larger induction port allowed more drug substance to enter the ACI which may be advantageous in some PSD work.

Metered-Dose Inhaler Salbutamol-Induced Tracheal Epithelial Lesions in Intubated Rabbits: Effects of the Site of Administration and Time

To determine (1) whether metered-dose inhaler (MDI) salbutamol administered at the elbow connector of the anesthetic circuit produced tracheal epithelial lesions in intubated rabbits, and (2) the time course for resolution of tracheal lesions produced by MDI salbutamol through an intratracheal catheter. Prospective, randomized, controlled trial. University-affiliated animal research laboratory. Thirty-nine adult New Zealand white rabbits. (1) Twenty-one intubated rabbits received 0,5, or 20 puffs of MDI salbutamol delivered at the elbow connector of the anesthetic circuit. (2) Eighteen intubated rabbits received five puffs of MDI salbutamol through an intratracheal catheter and were killed 1 h, 24 h, or 1 week later. Samples of trachea, bronchi, and lungs were examined by light microscopy, and the degree of epithelial injury was assessed semiquantitatively. MDI salbutamol (5 or 20 puffs) administered at the elbow did not induce tracheal epithelial injury. When administered through an intratracheal catheter, MDI salbutamol (five puffs) produced moderate or severe tracheal epithelial injury in those killed 1 h after the study. Evidence of epithelial regeneration was observed 24 h after the injury and recovery was virtually complete by 1 week. Epithelial lesions do not occur when the MDI salbutamol (5 or 20 puffs) is administered at the elbow connector of the ventilation circuit. Tracheal epithelial lesions produced by MDI salbutamol (five puffs) administered through an intratracheal catheter resolve within 1 week of the injury.

Factors affecting total and "respirable" dose delivered by a salbutamol metered dose inhaler.

Many factors contribute to the high variability of doses delivered to the lungs of patients using metered dose inhalers (MDIs). Relatively little attention has been paid to the contribution to this variability of the way in which the MDI is handled before the inhalation manoeuvre. Instruction leaflets often recommend procedures at odds with those used for in vitro testing of the device. The standard protocol for in vitro assessment of salbutamol MDIs involves shaking the MDI vigorously for 30 seconds and wasting the first two actuations. Subsequent actuations are introduced into the testing device at five second intervals. Patient instructions do not include a recommendation to waste the first two actuations and recommend a delay of one minute between actuations. A series of experiments was performed to determine whether such differences might be important. The total and "respirable" doses delivered by a salbutamol MDI (Ventolin, Allen & Hanburys) under various conditions were assessed with a multistage liquid impinger. The quantity of drug deposited on each stage was measured by an ultraviolet spectrophotometric method. The effect on the delivered dose of not shaking the canister, not wasting the first two doses, waiting 30 seconds between actuations, and using multiple rapid actuations was assessed by comparing the results with those obtained using the standard in vitro testing protocol. Compared with a standard protocol, it was found that not shaking the MDI before use reduced the total and "respirable" dose by 25.5% and 35.7%, respectively. The dose delivered when actuating the MDI at 30 second intervals was no different from that when intervals was no different from that when intervals of five seconds were used. Two actuations separated by one second had no effect on the total dose but reduced the "respirable" dose by 15.8%, while four rapid actuations reduced the total and "respirable" doses by 8.2% and 18.2%, respectively. Storing the MDI stem down reduced the total and "respirable" dose delivered in the first actuation by 25.0% and 23.3% despite shaking the MDI before use. MDIs containing drug in suspension must be shaken before use to resuspend the drug contained in the MDI, but shaking does not alter the composition of the suspension in the metering chamber and hence the dose in the first actuation remains low. Very rapid actuations can reduce the dose delivered per actuation, but salbutamol MDIs can be actuated immediately after a 10 second breath holding pause without affecting the dose delivered.

High-dose MDI salbutamol treatment of asthma in the ED

Beta-adrenergics have long been under special scrutiny because of their potential for cardiotoxicity. To assess the safety of high doses of salbutamol delivered by metered dose inhaler (MDI) with spacer in the emergency department (ED) setting, 11 patients (mean age 33 ± 12.2 years) with severe acute asthma were studied. All patients were treated with 400 μg of salbutamol at 10-minute intervals for 3 hours (1,200 μg each 30 minutes or 7,200 μg at 180 minutes. There were dose-related significant increases in forced expiratory volume in the first second (FEV 1) and peak expiratory flow (PEF) ( P < .01), with a net mean increase of 90.4% and 80.1%, respectively. A significant ( P < .01) reduction of heart rate was observed with treatment. At the end of protocol, reductions ranged from 7 beats/min to 35 beats/min (mean decrease 10.6 ± 10.5 beats/min). There was no prolongation in the QT c interval. Mean baseline serum potassium was 4.23 ± 0.53 mmol/L and decreased nonsignificantly after treatment to 3.99 ± 0.62 mmol/L. Only 4 patients showed net decreases. There were no significant changes in oxygen saturation and plasma glucose. The mean end-treatment salbutamol level was 10.0 ± 1.67 ng/mL. These data support the notion that treatment of acute asthma patients in the ED with 2.4 mg salbutamol per hour delivered by MDI and spacer produce satisfactory bronchodilation, low serum concentration, and minimal extrapulmonary effects.

Comparison between sodium cromoglycate (MDI: metered‐dose inhaler) and beclomethasone dipropionate (MDI) in treatment of adult patients with mild to moderate bronchial asthma A double‐blind, double‐dummy randomized, parallel‐group study

This study compared the efficacy and tolerability of sodium cromoglycate (SC) and beclomethasone dipropionate (BDP) in adult patients with bronchial asthma inadequately treated with bronchodilators alone. The study was a double-blind, randomized, double-dummy, parallel-group study. Patients with mild to moderate symptomatic asthma, inadequately treated with bronchodilators only, were, after a 2-week run-in (base-line) period, randomized to 8 weeks of treatment with either SC 10 mg four times daily or BDP 100 micrograms four times daily. Salbutamol metered-dose inhaler was given as relief medication. A total of 37 patients were randomized for treatment, 19 patients in the SC group and 18 patients in the BD group. Efficacy and safety were determined by daily record card data: morning and evening peak-expiratory-flow rates (PEFR), daytime and nighttime asthma symptom scores, and rescue salbutamol use. At clinic visits, FEV1 and FVC were measured, as were the physician's and the patient's assessment of the medication at the end of the study. The safety and tolerability of the trial medication were assessed by monitoring adverse events throughout the study. A clinically and statistically significant improvement of the asthma in FEV1, symptom scores, rescue medication, and global opinion of efficacy was observed, and both groups provided equivalent efficacy. The morning PEFR as well as the evening PEFR for both groups improved, but was statistically significant only for the BDP group (M-PEFR). Both drugs were well tolerated with only a few minor adverse events. This trial shows that SC and BDP are equally effective anti-inflammatory treatments for mild to moderate bronchial asthma in adults.

Improved method to label beta-2 agonists in metered-dose inhalers with technetium-99m

Labelling beta-2 agonists in a metered-dose inhaler (MDI) with technetium-99m allows imaging of the depostition of the aerosol in the respiratory tract. We have developed an improved labeling method in which anhydrous pertechnetate is dissolved in a small volume of ethanol, diluted with a fluorocarbon, and introduced into a commercial MDI. Imaging the MDI demonstrated that the 99mTc was associated with the active ingredient, not just the propellant. The method has been used successfully with salbutamol and fenoterol MDIs and should be directly applicable to other MDIs which contain hydrophilic drugs.

Dosing Efficiency and Particle-size Characteristics of Pressurized Metered-dose Inhaler Aerosols in Narrow Catheters

An experimental in vitro model was used to determine the effects of intraluminal catheter diameter and length on the delivered dose and particle-size characteristics of salbutamol (albuterol) aerosol delivered by metered dose inhaler (MDI) (Ventolin, 100 micrograms per puff). The dose of aerosolized drug that exited a 16-cm-long tracheal tube with an inner diameter (ID) of 6 mm was compared with that from 4 catheters of differing diameters and lengths that were inserted individually into the tracheal tube. The salbutamol MDI canister was actuated ten times into each delivery system, and the effluent aerosol was trapped onto a filter. The filtrate was dissolved in methanol, and the salbutamol concentration was determined using high-performance liquid chromatography. For the 3 22-cm-long catheters, the delivered dose (mean +/- SD) of salbutamol per actuation for the 22-standard wire gauge (SWG) catheter was 97.5 +/- 3.9 micrograms, which was similar to that for the 19-SWG catheter (102.3 +/- 2.5 micrograms) but was significantly less than that for the 14-SWG catheter (108.2 +/- 4.2 micrograms) (p < 0.05). These delivered doses exceeded those of the 6.0-mm-ID tracheal tube alone (2.33 +/- 0.76 micrograms) and the 13-cm-long 19-SWG catheter (2.17 +/- 0.29 micrograms) (p < 0.001). In a second experiment using a cascade impactor, the distribution of aerosol particle diameters that exited the 6-mm-ID tracheal tube was compared with that exiting a 13-cm-long 19-SWG catheter that extended halfway down the tracheal tube and with that exiting a 22-cm-long 19-SWG catheter inserted into the distal end of the 6-mm-ID tracheal tube. The mass median aerodynamic diameter (mean +/- SD) of the salbutamol aerosols delivered through both the 6.0-mm-ID tracheal tube (1.1 +/- 0.1 microns) and that of the 13-cm-long 19-SWG catheter (1.2 +/- 0.2 microns) were significantly less than that delivered through the 22-cm-long 19-SWG catheter (2.0 +/- 0.1 microns) (p < 0.05). The authors conclude that delivery of respirable aerosol can occur through narrow catheters that function as extended nozzles for MDIs. Optimal dosing will be obtained when the catheter extends the full length of the tracheal tube.