Titolo del documento

Electrostatics and inhaled medications: influence on delivery via pressurized metered-dose inhalers and add-on devices

Autori e Nazionalità

Mitchell JP, Chem C, Coppolo DP, Nagel MW. Canada

Fonte bibliografica

Respiratory Care 2007;52:283-300

Lingua

Inglese

Abstract

The movement of inhaler-generated aerosols is significantly influenced by electrostatic charge on the particles and on adjacent surfaces. Particle charging arises in the aerosol formation process. Since almost all inhalers contain nonconducting components, these surfaces can also acquire charge during manufacture and use. Spacers and valved holding chambers used with pressurized metered-dose inhalers to treat obstructive lung diseases are particularly prone to this behavior, which increases variability in the amount of medication available for inhalation, and this is exacerbated by low ambient humidity. This may result in inconsistent medication delivery. Conditioning the device by washing it with a conductive surfactant (detergent) or using devices made of charge-dissipative/conducting materials can mitigate electrostatic charge. This review discusses sources of electrostatic charge, the processes that influence aerosol behavior, methods to mitigate electrostatic charge, and potential clinical implications.

PMID

PMID: 17328827 [PubMed - indexed for MEDLINE]

Tipo di studio

Revisione narrativa

Livello di evidenza

Commento

Questa revisione è un interessante carellata sulle cause delle cariche elettrostatiche, i processi che le determinano, i metodi per ridurle e le potenziali implicazioni cliniche.

Titolo del documento

Determining factors of aerosol deposition for four pMDI- spacer combinations in an infant upper airway model

Autori e Nazionalità

Janssens HM, Krijgsman A, Verbraank TF, Hop WC, de Jongste JC, Tiddens HA.Olanda

Fonte bibliografica

J Aerosol Med 2004;17(1):51-56

Lingua

Inglese

Abstract

The aim of this study was to measure and compare the influence of tidal volume (Vt) respiratory rate (RR) and pMDI/spacer combination on aerosol deposition of 4 pMDI/spacer combinations, which are used for infants. An anatomically correct upper airway model of a 9-month-old infant was connected to a breathing simulator. Sinusoidal breathing patterns were simulated with; duty cycle T(i)/T(tot) = 0.42, Vt: 25, 50, 75, 100, 150, 200 ml (RR: 30 breaths/min); and RR: 20, 30, 42, 60, 78 breaths/min (Vt: 100 mL). pMDI/Spacers tested were: budesonide 200 microg/Nebuchamber, fluticasone 125 microg/Babyhaler and both budesonide and fluticasone with Aerochamber. Plastic spacers were detergent coated to reduce electrostatic charge. Spacer-output and lung dose were measured by a filter positioned between spacer and facemask or between model and breathing simulator. Particle size distribution of lung dose was assessed with an impactor during simulated breathing. Spacer-output was significantly positively correlated with Vt for all pMDI/spacers (all R > 0.77, p < 0.001), but not correlated with RR. Lung doses initially increased from Vt = 25 to 50 mL (Nebuchamber, Aerochamber) or to 100 mL (Babyhaler) and then decreased, with increasing Vt and RR (R: -0.98 to -0.82, p < 0.001). Lung doses of fluticasone were 1.5-6-fold higher compared with budesonide, irrespective of spacer type (p < 0.001). MMAD decreased with increasing Vt and RR. Dose to the lungs of particles <2.1 microm was independent of Vt and RR. Lung dose decreases with increasing inspiratory flow (increasing Vt or RR) by increasing impaction of coarse particles in the upper airways. Deposition of particles <2.1 microm is relatively flow independent. When electrostatic charge of spacers is reduced, lung dose is pMDI dependent and spacer independent.

PMID

15120013 [PubMed - indexed for MEDLINE]

Tipo di studio

Oseervazionale

Livello di evidenza

3

Commento

Titolo del documento

Electrostatic charge on spacer devices and salbutamol response in young children.

Autori e Nazionalità

Dubus JC, Guillot C, Badier M. Francia

Fonte bibliografica

Int J Pharm 2003;261:159-64

Lingua

Inglese

Abstract

Electrostatic charge on plastic spacer devices may affect the efficacy of inhaled drugs, but its consequences have never been evaluated in asthmatic children with airflow limitation. At the end of a positive metacholine challenge, 64 children (51.3+/-12.9 months, 32 boys, specific airway resistance (SRaw) 257.1+/-56.7% and forced expiratory volume in 1s (FEV(1)) 64.2+/-17.9% of the predicted value) inhaled one puff of hydrofluoroalkane-134a (HFA-134a) salbutamol (Ventoline((R))), and 15min later two other puffs (total dose of 300 microgram), delivered through either a new static Babyhaler((R)) (n=21), a detergent-coated, reduced static, Babyhaler((R)) (n=20), or a metal NES-Spacer((R)) (n=23) equipped with facemask. SRaw and FEV(1) were measured after each treatment and compared between groups by a Kruskal-Wallis test. The first 100 microgram salbutamol induced a 151.7+/-43.9% decrease in SRaw and a 19.9+/-10.6% increase in FEV(1). Additional 200 microgram salbutamol allowed a supplementary decrease of 35.1+/-25.7% in SRaw and increase of 12.1+/-11.8% in FEV(1), without significant difference between the spacer devices. Electrostatic charge on spacer devices does not affect bronchodilation with HFA-134a salbutamol in metacholine-challenged pre-school children. This could be in part explained by the use of supramaximal doses of salbutamol.

PMID

12878405 [PubMed - indexed for MEDLINE]

Tipo di studio

Osservazionale

Livello di evidenza

3

Commento

Studio che esamina le conseguenze delle cariche elettrostatiche in bambini asmatici con broncoostruzione

Titolo del documento

Effect of detergent-coated versus non-coated spacers on bronchodilator response in children with asthma

Autori e Nazionalità

Barben JU, Roberts M, Robertson CF. Australia

Fonte bibliografica

J Paediatr Child Health 2003;39:270-273

Lingua

Inglese

Abstract

OBJECTIVE: Previous studies have demonstrated that coating spacers with ionic detergents minimizes the static charge and thereby improves in vivo drug deposition. The present study aims to examine the effect of coated spacers versus non-coated spacers in the clinical situation. METHODS: A randomized, double-blind study in children with asthma and a ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) of < or =72% predicted was carried out. Spirometry was performed at baseline and at 10 min and 20 min after inhalation of two puffs of salbutamol (100 microg/puff) through either a detergent-coated or a non-coated spacer. RESULTS: Fifty children were studied (mean age 11.6 years, range 7-18 years): 26 in the group using coated spacers (CG); and 24 in the group using non-coated spacers (NCG). The mean percentage change in FEV1 from baseline 10 min after inhalation was 18.8% (range 5-50%) in the CG versus 18.5% (range 3-35%) in the NCG. At 20 min after inhalation, the per cent increase in FEV1 was 19.8% (range 0-50%) in the CG versus 19.5% (range 9-35%) in the NCG. There was no significant difference between groups in the percentage change in FEV1 after 10 min (P = 0.91), or after 20 min (P = 0.93). CONCLUSIONS: There was no improvement in bronchodilatation from detergent-coated spacers in the present study, possibly because a maximal bronchodilator response was achieved with the lower output.

PMID

12755932 [PubMed - indexed for MEDLINE]

Tipo di studio

Randomizzato, in doppio cieco

Livello di evidenza

1+

Commento

Gli autori non trovano alcun vantaggio nella risposta al bronciìodilatatore, misurata con il FEV1 fra un distanziatore sottoposto a trattamento antistatico e non. Gli autori ipotizzano che la massima risposta viene raggiunta con una quota di farmaco inferiore a quella utilizzata (è sufficiente poco salbutamolo per ottenere la risposta massimale)

Titolo del documento

Factors affecting the efficiency of aerosol therapy with pressurised metered-dose inhalers through plastic spacers

Autori e Nazionalità

Chuffart AA, Sennhauser FH, Wildhaber JH. Svizzera

Fonte bibliografica

Swiaa Med Wkly 2001;131:14-18

Lingua

Inglese

Abstract

AIM: The main objective of this study was to compare the in vitro delivery of salbutamol from a chlorofluorocarbon(CFC)-propelled pressurised metered-dose inhaler (pMDI) versus a newly developed hydrofluoroalkane(HFA)-propelled pMDI through various spacers. In addition, we aimed to study the effect on bronchodilator response when using an optimal pMDI/spacer combination for aerosol delivery compared to a suboptimal combination. METHODS: Particle size distribution and output from salbutamol pMDIs containing either CFC propellants (Ventolin) or HFA propellants (Airomir) were measured using a multistage liquid impinger (MSLI) and compared to that through both detergent-coated (non-static) or untreated (static) large volume (Nebuhaler, Volumatic) and small volume (Aerochamber) plastic spacers. Flow-volume curves (FEV1) were obtained from twelve asthmatic children with known significant bronchodilator response (8 males), aged 13-17 years, randomly inhaling salbutamol from a CFC-pMDI through a static spacer (Nebuhaler) and from an HFA-pMDI through a non-static spacer (Nebuhaler). RESULTS: In vitro output of particles in the respirable range (< 6.8 microns) from HFA-pMDIs was significantly higher than that from CFC-pMDIs using various spacers. Removal of electrostatic charge increased output from CFC- and HFA-pMDIs through all spacers by 17-82%. The mean (SD) bronchodilator response after inhalation of salbutamol from a CFC-pMDI through a static spacer was 7.1% (6.3%) compared to 17.5% (7.9%) after inhalation from an HFA-pMDI through a non-static spacer (p = 0.002). CONCLUSIONS: Use of a newly developed HFA-propelled pMDI greatly improves drug delivery through spacers compared to a CFC-propelled pMDI. However, electrostatic charge in plastic spacers remains the key determinant limiting delivery of salbutamol from a pMDI through spacers, and can be reduced by soaking the spacer in a household detergent. Using an optimal pMDI/spacer combination leads to a significantly improved bronchodilator response.

PMID

11205181 [PubMed - indexed for MEDLINE]

Tipo di studio

Osservazionale

Livello di evidenza

3

Commento

Eseguire un lavaggio con detergente è fondamentale per ridurre le cariche elettrostatiche dei distanziatori non conduttori fatti di plastica. Gli autori suggeriscono come questo procedimento dovrebbe essere eseguito 1 volta alla settimana

Titolo del documento

Randomised controlled study of clinical efficacy of spacer therapy in asthma with regard to electrostatic charge

Autori e Nazionalità

Dompeling E, Oudesluys-Murphy AM, Janssens HM, Hop W, Brinkman JG. Olanda 

Fonte bibliografica

Arch Dis Child 2001;84:178-182

Lingua

Inglese

Abstract

BACKGROUND: Inhalation therapy using a pressured metered dose inhaler (pMDI) and a spacer is frequently used in the treatment of airway disease in children. Several laboratory studies found a clear negative influence of electrostatic charge (ESC) on plastic spacers on the delivery of aerosol. AIMS: To investigate whether ESC on plastic spacers could diminish bronchodilating responses to salbutamol. METHODS: Ninety asthmatic children (aged 4-8 years) were randomised into three groups: metal Nebuchamber, plastic Volumatic, and plastic Aerochamber. The bronchodilating response was measured by the change in peak expiratory flow rate (PEF) after 100 microgram and 400 microgram salbutamol. Within the Volumatic and Aerochamber groups, a crossover comparison was made between electrostatic and non-electrostatic spacers. RESULTS: We found no significant effect of ESC on the bronchodilating response to salbutamol with any of the doses in the Aerochamber and Volumatic groups. For the plastic spacers, the mean difference of the change in PEF after 100 microgram salbutamol between non-electrostatic and electrostatic spacers was only +1.7% (95% CI -1.3% to 4.7%). After 400 microgram salbutamol this was +1.9% (95% CI -1.4% to 5.1%). A comparable efficacy was found for the Nebuchamber, the Aerochamber, and Volumatic with respect to the change in PEF after 100 and 400 microgram salbutamol. CONCLUSION: This study showed no negative influence of ESC on plastic spacers with regard to clinical efficacy of a beta(2) agonist (salbutamol) in children with asthma. The metal Nebuchamber, plastic Aerochamber, and plastic Volumatic were equally effective.

PMID

11159302 [PubMed - indexed for MEDLINE]

Tipo di studio

Studio Clinico Randomizzato in aperto, cross over

Livello di evidenza

2 +

Commento

Titolo del documento

Aerosol delivery from spacers in wheezy infants : a daily life study 

Autori e Nazionalità

Janssens HM, Heljnen EM, de Jong VM, Hop WC, Holland WP, de Jongste JC, Tiddens HA . Olanda 

Fonte bibliografica

Eur Respir J 2000;1685).850-6.

Lingua

Inglese

Abstract

The aims of this study were to assess and compare dose delivery and dose variability of pressurized metered dose inhalers (pMDI)/spacers in wheezy infants in daily life and to investigate factors influencing aerosol delivery. In an open randomized crossover study in 25 wheezy infants aged 5-26 months, a metal spacer (Nebuchamber), a detergent coated (DC) and a non-detergent coated (nonDC) plastic spacer (Babyhaler) were tested at home for 7 days each. Budesonide (200 microg b.i.d) was administered via a Nebuchamber or fluticasone (125 microg b.i.d) via a Babyhaler. Aerosol was trapped in filters, positioned between the spacer and face mask. Cooperation was scored on diary cards. Electrostatic charge (ESC) of the spacers was measured. Evaluations of the administration technique were made from video recordings. Median (range) dose delivery of the filters expressed as per cent (%) of nominal dose, was 34% (3-59), 23% (1-49), and 41% (12-55) for the Nebuchamber, nonDC-Babyhaler, and DC-Babyhaler respectively. Considerable dose variability was found, median (range) within-subject dose variability, expressed as coefficient of variation, for the Nebuchamber (49% (15-249)) was significantly higher when compared with both nonDC- (36% (12-325)) and DC-Babyhalers (27% (10-122)), for which dose variabilities were similar. Detergent coating was effective to reduce electrostatic charge, and to increase dose delivery, but had no effect on dose variability. Bad cooperation was an important cause for high dose variability for all spacers (r=0.5-0.6, p<0.02). Many mistakes were made during the administration procedure.

PMID

11153582 [PubMed - indexed for MEDLINE

Tipo di studio

Randomizzato in aperto, di tipo cross over 

Livello di evidenza

2+

Commento

Il rivestimento con un detergente è efficace nel ridurre le cariche elettrostatiche, ma non ha effetto sulla variabilità della dose. Molti errori sono stati eseguiti durante l'inalazione

Titolo del documento

Lung deposition of a aerosol-a comparison of different spacers

Autori e Nazionalità

Zar HJ, Weinberg EG, Binns HJ, Gallie F, Mann MD. Sud Africa 

Fonte bibliografica

Arch Dis Child 2000;82:495-498

Lingua

Inglese

Abstract

AIMS: To investigate (1) aerosol lung deposition obtained from two small volume conventional spacers (Babyhaler and Aerochamber) and a home made spacer (modified 500 ml plastic cold drink bottle); (2) the effect of using a face mask or mouthpiece; and (3) the relation between age and pulmonary deposition. METHODS: Lung deposition of aerosolised technetium-99m DTPA inhaled via spacer was measured in 40 children aged 3-7 years with stable asthma. Each patient performed sequential randomly assigned inhalations using two spacers. Three studies were performed: Babyhaler compared to Aerochamber (with facemasks); Babyhaler with facemask compared to Babyhaler with mouthpiece; and Babyhaler with mouthpiece compared to a 500 ml bottle. RESULTS: Median lung aerosol deposition from a Babyhaler and Aerochamber with masks were similar (25% v 21%, p = 0.9). Aerosol lung deposition from a Babyhaler with mask compared to a Babyhaler with mouthpiece was equivalent (26% v 26%, p = 0.5). Lung deposition was higher from a 500 ml bottle compared to a Babyhaler in both young (25% v 12.5%, p = 0.005) and older children (42% v 22.5%, p = 0.003). A notable reduction in pulmonary deposition occurred at 50 months of age. CONCLUSION: A Babyhaler or Aerochamber produce equivalent lung deposition of aerosol. There is no difference in lung deposition when a mask or mouthpiece is used. A modified 500 ml plastic bottle produces greater pulmonary aerosol deposition than a conventional small volume spacer.

PMID

10833188 [PubMed - indexed for MEDLINE]

Tipo di studio

sperimentale, di laboratorio

Livello di evidenza

Commento

Una bottiglia di plastica delle bibite, modificata una deposizione polmonare maggiore di un distanziatore convenzionale

Titolo del documento

Washing plastic spacers in household detergent reduces electrostatic chrage and greatly improves delivery 

Autori e Nazionalità

Piérart F, Wilhaber JH, Vrancken I, devadason SG, Le Souef PN. Australia 

Fonte bibliografica

Eur respir J 1999;13:637-638

Lingua

Inglese

Abstract

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.

PMID

10232445 [PubMed - indexed for MEDLINE]

Tipo di studio

Osservazionale

Livello di evidenza

3

Commento

i detersivi casalinghi offrono una soluzione efficace e poco costosa per ridurre le cariche elettrostatiche dentro i distanziatori

Titolo del documento

Variability of aerosol delivery via spacer devices in young asthmatic children in daily life 

Autori e Nazionalità

Janssens HM, Devadason SG, Hop WC, Le Souef PN, de Jongste JC,Tiddens HA

Fonte bibliografica

Eur Respir J 1999;13(4):787-9

Lingua

Inglese

Abstract

Pressurized metered dose inhalers (pMDI) are widely used together with spacers for the treatment of asthma in children. However, the variability of daily medication dose for pMDI/spacer combinations is not known. Electrostatic charge is a potential source of dose variability. Metal spacers have no static charge. This study assessed and compared within-subject variability of aerosol delivery of metal and plastic spacers. This was a randomized, crossover study in children with stable asthma aged 1-4 (group I, n=17) and 5-8 (group II, n=16) yrs. In both groups the amount of drug delivered to the mouth by a metal spacer (Nebuchamber) and one of two plastic (polycarbonate) spacers, i.e. Babyhaler in group I and Volumatic in group II was measured. The metal and plastic spacers were tested at home in a randomized order for 7 days each, using budesonide (200 microg b.i.d.). Aerosol was collected on a filter positioned between spacer and facemask or mouth. Budesonide on the filter was assessed by high performance liquid chromatography. The mean filter dose for each child (mean+/-SD) during the 7 days was expressed as a percentage of the nominal dose. Within-subject variability was expressed as coefficient of variation (CV). Mean filter dose in group I was 41.7+/-10.1% for Nebuchamber and 26.0+/-4.0% for Babyhaler (p<0.001). Mean filter dose in group II was 50.2+/-9.2% for Nebuchamber and 19.4+/-7.2% for Volumatic (p<0.001). Mean CV in group I was 34% for Nebuchamber and 37% for Babyhaler (p=0.44). Mean CV in group II was 23% for Nebuchamber and 34% for Volumatic (p=0.003). There was substantial within-subject dose variability in aerosol delivery in children using a pMDI/spacer at home. This variability was lower for the metal than for the plastic spacer in children 5-8 yrs of age. The dose delivered to the mouth was about two-fold higher for the metal than the plastic spacer independent of age

PMID

10362041 [PubMed - indexed for MEDLINE]

Tipo di studio

Studio osservazionale eseguito in laboratorio

Livello di evidenza

2 +

Commento

La dose di budesonide, somministrata con lo spray nella Nebuchamber di metallo che arrivava alla bocca era 2 volte superiore a quella che era possibile ottenere con il Volumatic di plastica

Kenyon CJ, Thorsson L, Borgstrom L, Newman SP. Gran Bretagna 

Eur Respir J 1998;11:606-610.

Inglese

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.

9596110 [PubMed - indexed for MEDLINE]

Osservazionale

3

Titolo del documento

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

Autori e Nazionalità

Wildhaber JH, Devadason SG, Eber E, Hayden MJ, Everard ML, Summers QA, LeSouef PN. Australia

Fonte bibliografica

Thorax 1996;51:985-8

Lingua

Inglese

Abstract

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.

PMID

8977597 [PubMed - indexed for MEDLINE]

Tipo di studio

Osservazionale

Livello di evidenza

3

Commento

Il ritardo nell'inizio dell'inspirio e l'esecuzione di spruzzi multipli causano una riduzione del 40.7% e del 76% rispettivamente nell'erogazione delle particelle aerosoliche più piccole