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Stable increased formulation atomization using a multi-tip nozzle device

Drug Delivery and Translational Research volume 8, pages 1815–1827 (2018)Cite this article

Abstract

Electrohydrodynamic atomization (EHDA) is an emerging technique for the production of micron and nano-scaled particles. The process often involves Taylor cone enablement, which results in a fine spray yielding formulated droplets, which then undergo drying during deposition. In this work, novel multi-tip emitter (MTE) devices were designed, engineered and utilized for potential up-scaled EHDA, by comparison with a conventional single-needle system. To demonstrate this, the active ketoprofen (KETO) was formulated using polyvinylpyrrolidone (PVP) polymer as the matrix material. Here, PVP polymer (5% w/v) solution was prepared using ethanol and distilled water (80:20) as the vehicle. KETO was incorporated as 5% w/w of PVP. Physical properties of resulting solutions (viscosity, electrical conductivity, density and surface tension) were obtained. Formulations were electrosprayed through both single and novel MTEs under EHDA conditions at various flow rates (5–300 μl/min) and applied voltages (0–30 kV). The atomization process using MTEs and single nozzle was monitored at using various process parameters via a digital optical camera. Resulting particles were collected 200 mm below processing heads and were analyzed using differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Digital recordings confirmed stable MTE jetting at higher flow rates. Electron micrographs confirmed particle size variation arising due to nozzle head design and evidenced stable jetting derived greater near-uniform particles. DSC, XRD and TGA confirm KETO molecules were encapsulated and dispersed into PVP polymer particles. In conclusion, novel MTE devices enabled stable atomization even at higher flow rates when compared to conventional single-needle device. This indicates an exciting approach for scaling up (EHDA) in contrast to current efforts focusing on multiple-nozzle and pore-based processing outlets.

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Acknowledgements

The authors would like to thank the EPSRC EHDA Network and The Royal Society (Industrial Fellowship) for their support.

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Authors and Affiliations

  1. The Leicester School of Pharmacy, De Montfort University, Leicester, LE1 9BH, UK

    Rita Haj-Ahmad, Manoochehr Rasekh, Kazem Nazari, Ekhoerose V. Onaiwu, Bushra Yousef & Zeeshan Ahmad

  2. Genvolt, New Road, Bridgnorth, Shropshire, WV16 6NN, UK

    Stuart Morgan & David Evans

  3. College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, 310027, China

    Ming-Wei Chang

  4. Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, 310027, China

    Ming-Wei Chang

  5. BlueFrog Design, 19 St. Margaret’s Street, Leicester, LE1 3EB, UK

    John Hall & Chris Samwell

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  1. Rita Haj-Ahmad
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  2. Manoochehr Rasekh
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  3. Kazem Nazari
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  4. Ekhoerose V. Onaiwu
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  6. Stuart Morgan
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  11. Zeeshan Ahmad
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Correspondence to Zeeshan Ahmad.

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Haj-Ahmad, R., Rasekh, M., Nazari, K. et al. Stable increased formulation atomization using a multi-tip nozzle device. Drug Deliv. and Transl. Res. 8, 1815–1827 (2018). https://doi.org/10.1007/s13346-018-0518-4

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Keywords

  • Multi-tip emitter (MTE)
  • Electrospraying
  • Nanoparticles
  • Microparticles
  • Jetting
  • Electrohydrodynamic
  • Encapsulation