Ionic detergents reduce electrostatic charge on plastic spacers, thereby improving in vitro drug delivery. The aim of this study was to gain practical information on the use of detergents and to evaluate the relevance of this information on in vivo drug deposition. Measurement of electrostatic charge and salbutamol particle size distribution was carried out on detergent-coated and noncoated plastic spacers. The efficiency of four household detergents was compared, and the influence of dilution and the duration of the antistatic effect were studied. In addition, the level of radiolabelled salbutamol deposition in the lungs of eight healthy adults was compared after inhalation through a new versus a detergent-coated spacer. In vitro, all tested detergents reduced the electrostatic charge on the spacer surface. This resulted in a mean increase of 37.4% (range 33.5-41.2) in small particle (<6.8 microm) salbutamol output compared with water-rinsed/drip-dried spacers. Dilution had no influence on the results and the effect lasted for at least four weeks. In vivo, the mean lung deposition of radiolabelled salbutamol in healthy subjects was 45.6% (range 43.4-49.5) through a detergent-coated spacer compared to 11.5% (range 7.6-17.9) through a static spacer (p<0.001). In conclusion, household detergents offer a simple and practical solution to the problem of static on plastic spacers and significantly improve both in vitro and in vivo delivery of salbutamol.

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 pm) 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 gm) particle delivery. Delay and multiple actuations resulted in a decrease of 40.7% and 76.0%, respectively, in small (<6.8 tm) 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 ofplastic 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. (Thorax 1996;51:985-988)

Several in vitro and in vivo studies have emphasized the importance of generating a high inspiratory flow when using a dry powder inhaler. Little attention has been paid to the influence of the inspiratory flow profile on the particle size distribution contained in aerosols generated by these devices. The internal volume of a device such as the Turbuhaler is small compared with a vital capacity breath and it is possible that all the powder has been drawn from the device before peak inspiratory flow has been achieved, particularly if the time to peak inspiratory flow is prolonged. A series of experiments were performed to assess the effect of different flow profiles through the Turbuhaler, each with a peak flow of 60 1 min-1. A 400 microgram budesonide Turbuhaler was enclosed in a chamber allowing air to pass unimpeded through the dosing channels and entrainment ports. A large three-way tap was used to blow powder from the device across a Malvern Mastersizer laser particle sizer which produced a profile of the particle size distribution within the aerosol. The rate of increase in flow through the Turbuhaler was determined by the rate at which the three-way tap was turned, and recorded by means of a pneumotachograph. The rate of increase in flow was found to significantly affect the particle size-distribution within the aerosol. Failure to attain a flow of 30 1 min-1 before 150 ml of air had passed through the device resulted in the aerosol volume median diameter increasing from less than 6.6 microns to greater than 45.3 microns. These results indicate that flow during the initial part of the inspiratory effort may be important in determining the characteristics of the aerosol generated by a dry powder inhaler. With more sophisticated equipment, it might be possible to explore the relationship between flow profile and particle size distribution generated by dry powder devices in more detail.

E El le ec ct tr ro os st ta at ti ic c c ch ha ar rg ge e o on n a a p pl la as st ti ic c s sp pa ac ce er r d de ev vi ic ceABSTRACT: The aim of this study was to determine whether electrostatic charge on a plastic spacer decreases the delivery of salbutamol from a pressurized metereddose 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 µm) 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.

QVAR TM , an extrafine hydrofluoroalkane/beclomethasone dipropionate formulation, has been shown to double lung deposition in adults. The aim of the present study was to assess the total body deposition and distribution of technetium99m-labelled ( 99m Tc) QVAR TM in children after inhalation via an Autohaler TM . Sixteen male asthmatic children (5-14 yrs) inhaled labelled drug (v4 MBq 99m Tc; 100 mg beclomethasone dipropionate) via an Autohaler within 30 min after salbutamol (200 mg) administration. Simultaneous anterior and posterior planar scintigraphic scans (120 s acquisition time) were collected after inhalation of labelled drug.Mean¡SD lung deposition of labelled drug (attenuation-corrected; percentage of ex-actuator dose) was 36.9¡9.2, 46.5¡11.6 and 54.1¡10.7% in children aged 5-7, 8-10 and 11-14 yrs, respectively. Combined oropharyngeal and gastrointestinal deposition was 59.7¡8.2, 48.9¡12.3 and 40.3¡11.8%. Lung deposition positively correlated with the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Gastrointestinal dose negatively correlated with the FEV1, FVC, height and age.In older children (11-14 yrs), lung deposition was almost identical to that reported in adults using QVAR TM . In children aged 5-10 yrs, lung deposition using QVAR TM was greater than the levels measured using other commercial aerosol delivery systems. Oropharygeal and gastrointestinal deposition was inversely related to age.