Please cite this article in press as: Najlah, M., et al., A study of the effects of sodium halides on the performance of air-jet and vibrating-mesh nebulizers. Int J Pharmaceut (2013), http://dx.doi.org/10.1016/j.ijpharm.2013.08.023 ARTICLE IN PRESS G Model IJP 13574 1–8 International Journal of Pharmaceutics xxx (2013) xxx–xxx Contents lists available at ScienceDirect International Journal of Pharmaceutics j o ur nal ho me page: www.elsevier.com/locate/ijpharm A study of the effects of sodium halides on the performance of air-jet and vibrating-mesh nebulizers Mohammad Najlah a , Asma Vali b,c , Michael Taylor b,c , Basel T. Arafat b,c , Waqar Ahmed b,d , Q1 David A. Phoenix b , Kevin M.G. Taylor b,e , Abdelbary Elhissi b,c,∗ a Faculty of Pharmacy, Albaath University, Homs, Syria b Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston PR1 2HE, United Kingdom c School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom d School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, United Kingdom e Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom a r t i c l e i n f o Article history: Received 16 May 2013 Received in revised form 12 August 2013 Accepted 15 August 2013 Available online xxx Keywords: Aerosol Electrolyte Halide Polarizing ability Surface tension Nebulizer a b s t r a c t The influence of sodium halide electrolytes on aerosols generated from the Aeroneb Pro vibrating mesh nebulizer and the Sidestream air-jet nebulizer has been evaluated. Fluids with a range of concentrations of Na halides (i.e. NaF, NaCl, NaBr and NaI) were used as nebulizer solutions and their effect on aerosol properties such as total aerosol output, fine particle fraction (FPF), volume median diameter (VMD) and predicted regional airway deposition were investigated. For both nebulizers, the inclusion of electrolyte significantly enhanced the aerosol properties compared with HPLC grade (deionized) water. Aerosol out- put, FPF and aerosol fraction less than 2.15 m were directly proportional to electrolyte concentration. Furthermore, the proportion of aerosols that are likely to deposit in the oropharyngeal region, and the VMD of the droplets were inversely related to the electrolyte concentration for both nebulizers. In gen- eral, the inclusion of electrolytes had a greater impact on the aerosol properties of the vibrating-mesh nebulizer. In the Aeroneb Pro, NaI 2.0% (w/v) was the optimum solution as it generated the highest aerosol output, FPF and output fraction below 2.15 m with the lowest VMD and minimal predicted oropharyn- geal deposition. This was attributed to the polarizing ability of iodide ions present in the largest quantity at the air–water interface. This study has shown that the Aeroneb Pro vibrating-mesh device demonstrated greatly enhanced aerosol properties when halides were included in the nebulizer solutions. © 2013 Published by Elsevier B.V. 1. Introduction There are three types of nebulizers: ultrasonic, air-jet and vibrating-mesh nebulizers. In ultrasonic nebulizers, aerosol is gen- erated by a high frequency vibrating piezoelectric crystal producing a fountain at the air–liquid interface. The lower regions of the foun- tain emit small droplets, whilst large droplets are formed at the apex of the fountain (McCallion and Taylor, 2002). Baffles are placed in the nebulizer to trap large droplets and recycle them to the nebu- lizer reservoir (O’Callaghan and Barry, 1997). Ultrasonic nebulizers generate heat during atomization; they are generally inappropri- ate for the delivery of heat-labile materials such as proteins (Niven et al., 1995) and liposomes (Elhissi and Taylor, 2005). Traditional ultrasonic nebulizers are also inefficient for delivering suspensions (McCallion and Taylor, 2002) and viscous liquids (Elhissi and Taylor, ∗ Corresponding author at: Institute of Nanotechnology and Bioengineering, School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Pre- ston PR1 2HE, United Kingdom. Tel.: +44 1772895807; fax: +44 1772894956. E-mail addresses: aelhissi@uclan.ac.uk, aelhissi@yahoo.com (A. Elhissi). 2005). Air-jet nebulizers utilize the energy provided by compressed gas to generate an aerosol (O’Callaghan and Barry, 1997). However, air-jet nebulization causes the formation of solvent vapor which saturates the outgoing air (Ferron et al., 1976; Dennis et al., 1990; Smye et al., 1992). This cools the nebulizer fluid and results in an increase in solute concentration in the residual fluid (Cockcroft et al., 1989). The shortcomings of the air-jet and ultrasonic neb- ulizers may be overcome by using vibrating-mesh nebulizers. They have been shown to be suitable for the delivery of suspensions (Fink and Simmons, 2004), nucleic acids (Lentz et al., 2006) and nanomedicine formulations such as liposomes (Elhissi and Taylor, 2005; Elhissi et al., 2006, 2007, 2011) and niosomes (Elhissi et al., 2013). There are two types of vibrating-mesh nebulizers: passively vibrating mesh and actively vibrating mesh. Passively vibrating mesh devices (e.g. Omron MicroAir nebulizer) contain a mesh plate, with 6000 tapered holes, each having size of approximately 3 m (Ghazanfari et al., 2007). A piezoelectric crystal induces vibra- tions which are transmitted to an adjacent horn transducer; these “passive vibrations” cause the perforated mesh plate to vibrate, resulting in fluid extrusion through the mesh holes and aerosol 0378-5173/$ – see front matter © 2013 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.ijpharm.2013.08.023 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59