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Pharmaceutical aerosol electrostatics: a field with much potential for development “

The ultimate goal is to understand how physicochemical variables affect aerosol charging and use this knowledge to manipulate the charge profiles in order to control particle deposition in vivo, if charge can indeed affect deposition.



Keywords:  deposition • dry powder inhaler • electrostatic charge • inhalation • lungs • metered dose inhaler • nebulizer • particle • pharmaceutical aerosol • spacer

Electrostatics is the study of the properties and effects of stationary or slow-moving (nonaccelerated) charges in solids or liquids. The charging of solids has been known for many centuries. The ancient Greeks already observed that amber after rubbing can attract small, light objects such as straw or feathers [1] . However, despite the long history of awareness, many aspects of electrostatic phenomena are still unclear. In particular, knowledge on the fundamental mechanism and control of the charging of dielectrics (nonelectrically conducting materials) is poor. This is because contact charging, also known as triboelectrification, is complex and is affected by many factors such as relative humidity, temperature, surface impurities, surface roughness, contact area, and other physicochemical factors that are difficult to control [2] . Moreover, friction upon contact generates heat, which reduces the predictability of the resultant charges [2] . Electrostatics is pertinent to the pharmaceutical industry because numerous physical contacts occur between materials during manufacturing, packaging and handling. The charges generated are often retained on the materials because drugs, excipients and medical device components are almost always dielectrics. The electrostatic charges may influence the industrial processes mentioned above by affecting powder flow, mixing and dosing. They may also have an impact on drug delivery. The effect of electrostatic charges on pulmonary drug delivery has not been studied extensively. Reported studies in this field are

10.4155/TDE.14.96 © 2015 Future Science Ltd

relatively few, most of which were conducted within the last two decades. Nevertheless, electrostatic deposition has long been theorized to be one of the five major mechanisms of particle deposition in the airways, the other four being inertial impaction, gravitational sedimentation, diffusion and interception [3] . Charge affects deposition in two ways, namely, via space charge force and image charge force. Space charge force is the repulsion between charged particles of the same polarity in an aerosol cloud [4] . On the other hand, image charge force is the attraction between a charged particle and its image charge on a surface. Although the airways are normally neutral in charge, an image charge with the same magnitude but opposite polarity will be induced on the surface if a charged particle is positioned near that location [5,6] . The image charge will thus attract the particle to deposit on the airway surface. According to Coulomb’s law, electrostatic force is inversely proportional to the square of the distance between two charges. Therefore, electrostatic forces exerted by charged particles are expected to be significant inside the small dimensions of the airways. However, few in vivo studies on the effect of charge on particle deposition have been conducted. Furthermore, the data obtained were inconclusive. Melandri et al. [7,8] found that the deposition of inhaled monodisperse 0.3–1.1 μm carnauba wax particles in human subjects increased with the amount of charge carried, up to about 200 elementary charges per particle. Since only the net deposition

Ther. Deliv. (2015) 6(2), 105–107

Philip Chi Lip Kwok Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China Tel.: +852 3917 6335 pclkwok@ hku.hk

part of

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Editorial  Lip Kwok was measured in those studies, the specific location of particle deposition was unknown. It was assumed from the small particle size that the increase in deposition occurred in the alveoli [8] . Some in vitro and computational studies on electrostatic deposition have been reported. The deposition of monodisperse 15–125 nm salt particles with one positive elementary charge per particle was higher than that of neutral particles in a tubular model [9] and hollow airway cast [10] . Computational models using a dichotomous airway construct have also shown the trend of increasing deposition with charge. Balachandran et al. [6] found that when the number of elementary charges per particle was increased from 1 to 200 the deposition of 2.2 μm particles was increased in all airway generations. In the lower airways image charge forces were predominant and in the upper airways space charge forces. As the amount of charge was increased to half of Gauss’ limit (the maximum charge a particle can carry), most particles deposited in the upper airways as space charge forces overwhelmed [6] . Bailey  et al. obtained similar effects of electrostatic forces on deposition for 0.5 μm and 5 μm particles; however, contribution from space charge force was deemed unimportant and was not considered [5] . Human scintigraphic results of inhaled radiolabeled droplets from a nebulizer agreed with the model prediction regarding the total deposition and deposition in the head region, while in vivo alveolar deposition was higher than the simulated data [11] . However, the charges carried by the nebulized droplets were not stated. It should be noted that the results were reported largely empirically without details on the deposition sites of the charged particles. To improve the in vitro–in vivo correlation of electrostatic deposition, more thorough studies are needed.



This has significant regulatory and clinical implications so research in pharmaceutical aerosol electrostatics is expected to gain further interest and importance in the near future.



Another line of investigation examines the electrostatic properties of pharmaceutical aerosols. These studies characterized the charges carried by particles or droplets generated from inhalers. The influence of formulation and inhaler component variables on the generated charges was also evaluated. Most studies focused on dry powder inhalers (DPIs), metered dose inhalers (MDIs) and spacers. Only a few studies examined nebulizers. It was found that aerosols produced from pharmaceutical inhalers carried charges, the profiles of which were dependent on the drug, excipients (including propellants and moisture

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content in MDIs) and inhaler component materials  [12] . It is well known that electrostatic charges on the inner surfaces of spacers reduce the inhalable dose. Charged spacers essentially act as electrostatic filters that capture MDI particles carrying higher charges, thus increasing drug retention inside the spacers [13] . The elimination of spacer wall charges with a detergent coating significantly improves drug delivery. The estimated charge level of particles from DPIs and MDIs were high enough to affect deposition according to published computational data [12] . On the contrary, the charges of nebulized droplets may be too low to influence deposition [14] . It was also observed that the higher the ionic content of the liquid (i.e., electric conductivity), the lower the charges. The effect of relative humidity during storage and dispersion on the charges produced from DPIs is also formulation-dependent. The morphology and crystallinity of the particles may affect charging too  [15–17] . Studies on the relationship between various physicochemical factors and the electrostatic properties of pharmaceutical aerosols are still at an early stage. Due to the complexity of triboelectrification and difficulty in controlling the various factors, no universal trends applicable across formulation and inhaler component compositions have been identified. In fact, some variables are difficult to be controlled independently, such as morphology and crystallinity. Furthermore, observations obtained from the limited in vitro studies cannot be compared with each other due to differences in the formulations, inhalers and experimental conditions tested. Most of the studies conducted hitherto measured the net charge of particles, thus charges of the two polarities in the aerosol sample could not be discerned. Meanwhile, in vivo scintigraphic studies with robust control of particle size and charge are lacking. Such work is necessary for providing conclusive evidence on whether electrostatic charges could affect deposition in vivo because it is unclear whether the fully humidified air inside the lungs could dissipate the charges and consequently dampen or even negate the theoretical electrostatic effects. More extensive in vitro and in vivo studies are therefore required. There is certainly much potential for development. The ultimate goal is to understand how physicochemical variables affect aerosol charging and use this knowledge to manipulate the charge profiles in order to control particle deposition in vivo, if charge can indeed affect deposition. This has significant regulatory and clinical implications so research in pharmaceutical aerosol electrostatics is expected to gain further interest and importance in the near future.

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Pharmaceutical aerosol electrostatics: a field with much potential for development 

Financial & competing interests disclosure The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment,

References 1

Hendricks CD. Charging macroscopic particles. In: Electrostatics and its Application, Moore AD (Ed.). John Wiley & Sons, NY, USA ,57–85 (1973).

2

Bailey AG. Charging of solids and powders. J. Electrostat. 30, 167–180 (1993).

3

Hinds WC. Aerosol Technology: Properties, Behavior, and Measurement of Airborne Particles. John Wiley & Sons, NY, USA (1999).

4

Koolpiruck D, Prakoonwit S, Balachandran W. Numerical modeling of inhaled charged aerosol deposition in human airways. IEEE Trans. Ind. Appl. 40(5), 1239–1248 (2004).

5

Bailey AG, Hashish AH, Williams TJ. Drug delivery by inhalation of charged particles. J. Electrostat. 44(1–2), 3–10 (1998).

6

Balachandran W, Machowski W, Gaura E, Hudson C. Control of drug aerosol in human airways using electrostatic forces. J. Electrostat. 40–41, 579–584 (1997).

7

Melandri C, Prodi V, Tarroni G et al. On the deposition of unipolarly charged particles in the human respiratory tract. Inhaled Part. 4 Pt 1, 193–201 (1975).

8

Melandri C, Tarroni G, Prodi V, De Zaiacomo T, Formignani M, Lombardi CC. Deposition of charged particles in the human airways. J. Aerosol Sci. 14(5), 657–669 (1983).

9

Cohen BS, Xiong JQ, Asgharian B, Ayres L. Deposition of inhaled charged ultrafine particles in a simple tracheal model. J. Aerosol Sci. 26(7), 1149–1160 (1995).

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consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript. 10

Cohen BS, Xiong JQ, Fang CP, Li W. Deposition of charged particles on lung airways. Health Phys. 74(5), 554–560 (1998).

11

Bailey AG. The inhalation and deposition of charged particles within the human lung. J. Aerosol Sci. 42, 25–32 (1997).

12

Wong J, Chan H-K, Kwok PCL. Electrostatics in pharmaceutical aerosols for inhalation. Ther. Deliv. 4, 981–1002 (2013).

13

Kwok PCL, Collins R, Chan H-K. Effect of spacers on the electrostatic charge properties of metered dose inhaler aerosols. J. Aerosol Sci. 37(12), 1671–1682 (2006).

14

Kwok PCL, Trietsch SJ, Kumon M, Chan H-K. Electrostatic charge characteristics of jet nebulized aerosols. J. Aerosol Med. Pulm. Drug Deliv. 23, 149–159 (2010).

15

Murtomaa M, Harjunen P, Mellin V, Lehto V-P, Laine E. Effect of amorphicity on the triboelectrification of lactose powder. J. Electrostat. 56, 103–110 (2002).

16

Murtomaa M, Mellin V, Harjunen P, Lankinen T, Laine E, Lehto V-P. Effect of morphology on the triboelectrification in dry powder inhalers. Int. J. Pharma. 282, 107–114 (2004).

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Wong J, Kwok PCL, Noakes T, Fathi A, Dehghani F, Chan H-K. Effect of crystallinity on electrostatic charging in dry powder inhaler formulations. Pharma. Res. 31, 1656–1664 (2014).

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Pharmaceutical aerosol electrostatics: a field with much potential for development.

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