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)

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.

It is well accepted that control of airway inflammation is crucial for overall asthma control. Hence, efficient anti-inflammatory therapy is important for disease control. Therefore, we studied the effect of a treatment with montelukast on subjective and objective measures in preschool asthmatic children with insufficient control of airway inflammation, illustrated by increased fractional exhaled nitric oxide (FeNO). Thirty-one preschool children (2.5-5 years) were included in this study. Children with FeNO ! 10 ppb at the first visit received montelukast 4 mg as a first line therapy or an add-on therapy to their baseline treatment (group 1). Therapy was not changed at first visit in children with FeNO < 10 ppb (group 2). Symptom scores, FeNO, lung function (forced oscillation, Rrs8Hz) and airway responsiveness to adenosine 5 0 -monophosphate (AMP) were assessed at visits 1 and 2 eight weeks apart. There was a significant decrease in FeNO (median [interquartile range]; 12.9 [3.7] vs. 7.6 [6.85] ppb, P ¼ 0.011), Rrs8Hz (mean AE SD; 10.03 AE 3.1 vs. 8.72 AE 2.43 hPa.s/L; P ¼ 0.047) and symptom scores (2[2] vs. 1.5[2], P ¼ 0.034) and a significant increase in the provocative AMP dose (2.65 AE 2.1 vs. 4.54 AE 1.05; P ¼ 0.015) in group 1 but not in group 2. First line or add-on treatment of oral montelukast in preschool children with mild to moderate asthma and elevated FeNO, decreased levels of FeNO, improved airway responsiveness to AMP, lung function and symptom scores.Group 1: children with FeNO levels !10 ppb; Group 2: children with FeNO levels <10 ppb. 1 Mean AE standard deviation. 2 Chi-square. ICS, inhaled cortico-steroids.

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In current asthma guidelines, dosage regimens for inhalation therapy in children are based on adult doses and are generally titrated per kilogram of bodyweight or per square metre of body surface area. However, these recommendations do not correspond well with current knowledge of aerosol therapy in childhood. Lung deposition of the aerosolised drug is the key determinant for clinical efficacy and for systemic side effects of inhalation therapy. Lung deposition increases with age, whereas lung deposition expressed as a percentage per kilogram bodyweight is age-independent. This finding is explained by the self-regulating effect of age-dependent airway anatomy on lung deposition. Therefore, it is more likely that adult doses translate into paediatric doses only by virtue of the differences in self-limiting pulmonary deposition when using the same absolute nominal doses of the medication. Adapting the adult dose to a paediatric dose calculated on body size might be unnecessary and could lead to insufficient pulmonary deposition of medication. These findings suggest that dosage regimens for inhalation therapy for children may have to be reconsidered, and should be determined from dose-ranging studies rather than calculated from adult doses based on body size.

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