Biomedical subjects

S G Devadason

Publications and source records attributed to S G Devadason.

28 records · Page 2Linked to original sources

PubMed1997

Lung deposition from the Turbuhaler in children with cystic fibrosis.

Drug delivery to patients using dry powder inhalers, such as the Turbuhaler, is believed to be influenced by the inspiratory flow used. Clinical studies have indicated that this delivery system can be used effectively by children. However, it is not known how the total and weight-corrected dose delivered to the airways varies with age. A deposition study using technetium-99m (99mTc)-labelled budesonide was performed in order to determine the effect of age on delivery. Twenty one children with cystic fibrosis, aged 4-16 yrs, were recruited. They were clinically stable with normal lung function. Initially, a gamma camera scan was taken in front of a flood source containing 37 MBq of 99mTc. Subsequently, subjects inhaled through a low resistance inspiratory filter connected to a commercially available Turbuhaler. Immediately afterwards they inhaled from a noncommercial Turbuhaler containing budesonide labelled with 99mTc, and then underwent anterior and posterior gamma camera scans. Both Turbuhaler inhalers were attached to a portable spirometer and the peak inspiratory flow through the Turbuhaler was recorded for each inhalation. The total body dose was calculated from the dose deposited on the inspiratory filter connected to the commercial Turbuhaler. Analysis of the gamma camera images provided information on the proportion of the radiolabel delivered to the lungs compared to that deposited in the upper airway and stomach. As expected, a highly significant positive correlation was noted between the peak inspiratory flow generated by the patient through the Turbuhaler and the dose delivered to the lung. Similarly, there was a highly significant positive correlation between age and "total lung dose". However, when total lung dose was corrected for body weight, there was a nonsignificant negative correlation with age. This study suggests that the "weight-corrected lung dose" achieved when children aged > 6 yrs use the Turbuhaler, is largely independent of age. It would appear that the flow-dependent properties of this device are such that the reduced peak inspiratory flow generated by younger children results in a lower dose to the lungs, but that this is off-set by their lower body weight. This is unlikely to be a property of other devices with different flow/drug delivery characteristics.

Adolescent↗

PubMed1997

Comparison of drug delivery from conventional versus "Venturi" nebulizers.

Attempts to improve drug delivery from conventional jet nebulizers have included the use of storage systems to reduce drug wastage during exhalation. Venturi nebulizers enhance drug delivery during inhalation, reducing treatment times and drug wastage. This study investigated the effect of age on inhaled dose from a conventional jet nebulizer (Acorn) used both with and without a storage chamber (Mizer), compared to two Venturi nebulizers (Ventstream and Pari LC). Filters were attached to the four nebulizer systems, containing salbutamol, and 18 children with cystic fibrosis (3-16 yrs) inhaled through these devices. The quantity of drug collected on the filter was assessed using ultraviolet spectrophotometry. The particle size distribution of the aerosol from each nebulizer system was measured using laser diffraction. Inspiratory filter deposition using the Acorn was lower than the Acorn with Mizer, and both Venturi nebulizers. Filter deposition using the Acorn with Mizer was lower than the Pari LC. No trend with age, height or weight was noted using any nebulizer. Aerosol particle size using the Ventstream was lower than the other nebulizer systems. Drug output from both Venturi nebulizers was more efficient than from the jet nebulizer, used with and without the storage chamber, during inhalation by children with cystic fibrosis. The inhaled dose did not change with the patient's age or size using both types of nebulizer.

Administration, Inhalation↗

PubMed1996

In vitro assessment of drug delivery through an endotracheal tube using a dry powder inhaler delivery system.

BACKGROUND: Jet nubulisers and metered dose inhalers are widely used to deliver aerosolised drugs to the lungs of intubated patients in adult intensive care units. Drug delivery using these systems has been shown to be inefficient and both forms of delivery have the potential to induce paradoxical bronchoconstriction in patients with reactive airways disease. METHODS: Experiments were carried out to determine whether it was possible to deliver drug from a dry powder delivery system through an endotracheal tube. A 200 micrograms budesonide Turbohaler was enclosed in a chamber which allowed it to be inserted into a ventilator circuit. Experiments were performed with a multistage liquid impinger in which drug was drawn through the Turbohaler and endotracheal tube at 60 l/min providing an index of the maximum drug delivery achievable via this route. A second series of experiments was performed in which the Turbohaler was placed in a ventilator circuit using a Servo 900C volume cycled ventilator. Drug delivered from the Turbohaler during the inspiratory phase was collected on a filter placed between the end of a 9 mm endotracheal tube and a model lung. A tidal volume of 500 ml and inspiratory time of 0.5 seconds was used. Budesonide was assayed using an ultraviolet spectrophotometric assay. RESULTS: Thirty percent of the nominal dose passed through the endotracheal tube and was collected in the multistage liquid impinger. Mean drug delivery to the filter in the ventilator circuit was 20%. CONCLUSIONS: This in vitro study indicates that drugs from dry powder inhalers (in this case the Turbohaler) can be satisfactorily delivered through endotracheal tubes and that clinical evaluation of this technique is now indicated.

Aerosols↗

PubMed1996

Effect of electrostatic charge, flow, delay and multiple actuations on the in vitro delivery of salbutamol from different small volume spacers for infants.

BACKGROUND: A study was undertaken to determine the influences of electrostatic charge, flow, delay, and multiple actuations on the in vitro delivery of salbutamol generated by a pressurised metered dose inhaler (pMDI) from small volume spacers used in infants. METHODS: Ten actuations from a salbutamol pMDI were drawn at different flow rates after either single or multiple actuations, with or without delay, through either static or reduced static spacers. An ionic detergent was used to reduce the charge of plastic spacers (Babyhaler, Babyspacer, Aerochamber, Nebuhaler). Electrostatic charge was measured using an electrometer. A multistage liquid impinger was used to determine the particle size distribution of the output of the pMDI through the spacers. RESULTS: Electrostatic charge on the surface of plastic spacers had the greatest influence on delivery, causing a decrease in drug delivery. Reducing charge by coating the surface with ionic detergent resulted in an increase of 46.5-71.1% (p < 0.001) in small (< 6.8 microns) particle delivery from small volume plastic spacers. Lower flow, delay, and multiple actuations resulted in decreased delivery from static spacers. Lower flow resulted in a decrease of 15% in small (< 9.6 microns) particle delivery. Delay and multiple actuations resulted in a decrease of 40.7% and 76.0%, respectively, in small (< 6.8 microns) particle delivery. The influences of lower flow, delay, and multiple actuations were greatly reduced or even eliminated by reducing charge. However, multiple actuations still resulted in a significant decreased delivery (p < 0.05). The reduced static Nebuhaler had a higher delivery than all small volume spacers. CONCLUSIONS: Electrostatic charge has a major influence on the delivery of salbutamol from small volume spacers. Using a metal spacer or ionic detergent coating of plastic spacers resulted in no or reduced charge and hence in improved delivery. Lower flow, delay, and multiple actuations played a major part only in static spacers.

Albuterol↗

PubMed1996

Particle size selection device for use with the Turbohaler.

BACKGROUND: Drug deposited within the upper airways of patients using dry powder inhalers does not contribute to the therapeutic effect but can result in unwanted local side effects and, when swallowed, may contribute to systemic effects. A chamber has been devised which uses the centrifugal force generated by the Turbohaler to remove large "non-respirable" particles with a view to minimising deposition in the upper airway. An in vitro study was performed to determine whether such a chamber could reduce the dose contained in coarse particles without having a significant effect on the "respirable dose". METHODS: The mouthpiece of a 200 micrograms Turbohaler was modified to allow a small volume chamber to be attached. The particle size distribution generated by the Turbohaler was assessed using a multi-stage liquid impinger with a flow rate of 60 l/min. The quantity of drug on each stage was quantified using an ultraviolet spectrophotometric technique. For each experiment 10 actuations were used to ensure adequate quantities of drug on each stage. Particles depositing on stages 3 + 4 have a diameter of < 6.8 microns and are arbitrarily referred to as the "respirable dose". The particle size distribution obtained using the Turbohaler (n = 10) was compared with that from the Turbohaler+ chamber (n = 11). RESULTS: The addition of the chamber resulted in the mean (SD) dose contained in larger "non-respirable" particles depositing on stages 1 + 2 being reduced from 52.2 (12.3) to 29.6 (6.9) micrograms per actuation. However, the chamber did not affect the "respirable" dose. The dose contained in particles with a diameter of < 6.8 microns from the standard Turbohaler was 91.1 (8.9) micrograms compared with 82.4 (18.6) micrograms when used with the chamber. CONCLUSIONS: These results indicate that it is possible to devise an effective particle size selection device for the Turbohaler. It may be possible to produce such devices for other dry powder inhalers, although the design would need to be tailored to each particular device.

Aerosols↗

PubMed1996

Electrostatic charge on a plastic spacer device influences the delivery of salbutamol.

The aim of this study was to determine whether electrostatic charge on a plastic spacer decreases the delivery of salbutamol from a pressurized metered-dose inhaler (pMDI) and, if so, to find an optimal and practical treatment to remove the charge. Ten single actuations from a salbutamol pMDI were drawn through different Volumatic spacers at a constant flow of 60 L.min-1. The efficacies of different methods of removing charge were tested, including detergent coating of the spacers. A multistage liquid impinger was used to determine the particle size distribution of the output of the pMDI through the Volumatic spacers. The electrostatic charge on the inner surface of the spacers was measured both quantitatively with an electrometer, and qualitatively by the attraction of a thin strip of cellulose membrane to the wall of the spacer. Each experiment was repeated four times. Ionic detergent coating of the spacers removed the charge for at least 24 h. This resulted in an increase of 55-70% in small particle (< 6.8 microns) delivery compared to delivery from new spacers with high charge. We have demonstrated that electrostatic charge plays a major role in the delivery of salbutamol through plastic spacers. Adequate treatment with ionic detergent removes the charge and improves drug delivery.

Albuterol↗

PubMed1995

An alternative aerosol delivery system for amiloride.

BACKGROUND: The advent of novel treatments such as aerosolized amiloride are potentially useful additions to the therapeutic options available for the treatment of cystic fibrosis. Unfortunately, amiloride and other aerosolized drugs such as antibiotics are generally administered via jet nebulisers which are time consuming to use, and thus limit the acceptance and efficacy of these forms of treatment. In vitro experiments were performed in order to determine whether amiloride could be administered in dry powder form using a Turbohaler. METHODS: Amiloride was micronised and loaded into 200 micrograms Turbohalers. The dose delivered per actuation and particle size distribution of the generated aerosol were assessed using a flow of 60 l/min through the Turbohaler. The dose of amiloride delivered was measured by collecting the aerosol on a filter and the quantity of drug was assayed by an ultraviolet spectrophotometric method. The particle size distribution was assessed using a Malvern MasterSizer laser particle sizer and compared with that generated by a commercially available 200 micrograms budesonide Turbohaler. RESULTS: The mean (SD) dose delivered per actuation was 246.3 (40.4) micrograms. The volume median diameter of the amiloride aerosol was 3.80 (0.68) micron compared with 3.07 (1.47) microns for budesonide. CONCLUSIONS: These results suggest that therapeutic doses of micronised amiloride could be delivered effectively and conveniently as a dry powder aerosol using a Turbohaler.

Aerosols↗

PubMed1995

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Albuterol↗

PubMedDate not supplied

Improved efficiency of budesonide nebulization using surface-active agents.

Our aim was to improve the efficiency of nebulised budesonide using surface-active agents. Cationic, anionic, and nonionic detergents were added to commercial budesonide suspension, and the particle size distribution during nebulization was measured using both cascade impaction and laser diffraction. Our results showed that the emitted dose was increased after addition of cationic (p < 0.001) and nonionic detergents (p < 0.01) compared with the commercial formulation alone. The respirable fraction was increased for all detergent formulations (p < 0.001) compared with the commercial formulation. We concluded that cationic and nonionic detergent increased the total output of budesonide from the Sidestream. All detergent formulations increased the respirable fraction of nebulized budesonide.

Administration, Inhalation↗

PubMedDate not supplied

The Chocuhaler: sweet deliverance in asthma management.

OBJECTIVE: To determine the characteristics of a new cocoa-based edible spacer device for the delivery of aerosol bronchodilator. DESIGN: In-vitro comparison of two spacer devices (standard and edible) and determination of bronchodilator response using the edible spacer. SETTING: A university children's hospital in Western Australia. SUBJECTS: Two volunteers with moderate asthma. RESULTS: Compared with a standard spacer, the edible spacer delivered significantly more bronchodilator in droplets of a size likely to enter the respiratory tract. A significant bronchodilator response occurred in two out of two subjects when salbutamol was inhaled orally via the chocolate spacer. No significant bronchodilator response occurred in either subject when the spacer was eaten at the end of the study. CONCLUSION: The chocolate spacer used in this study is a suitable device to deliver salbutamol by inhalation. However, there may be potential drawbacks of weight gain in some patients and meltdown in hot climates.

Administration, Inhalation↗