Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography

Nicholas Mason-Smith, Daniel J. Duke, Alan L. Kastengren, Peter J. Stewart, Daniela Traini, Paul M. Young, Yang Chen, David A. Lewis, Julio Soria, Daniel Edgington-Mitchell, Damon Honnery

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Purpose: Typical methods to study pMDI sprays employ particle sizing or visible light diagnostics, which suffer in regions of high spray density. X-ray techniques can be applied to pharmaceutical sprays to obtain information unattainable by conventional particle sizing and light-based techniques. 

Methods: We present a technique for obtaining quantitative measurements of spray density in pMDI sprays. A monochromatic focused X-ray beam was used to perform quantitative radiography measurements in the near-nozzle region and plume of HFA-propelled sprays. 

Results: Measurements were obtained with a temporal resolution of 0.184 ms and spatial resolution of 5 μm. Steady flow conditions were reached after around 30 ms for the formulations examined with the spray device used. Spray evolution was affected by the inclusion of ethanol in the formulation and unaffected by the inclusion of 0.1% drug by weight. Estimation of the nozzle exit density showed that vapour is likely to dominate the flow leaving the inhaler nozzle during steady flow. 

Conclusions: Quantitative measurements in pMDI sprays allow the determination of nozzle exit conditions that are difficult to obtain experimentally by other means. Measurements of these nozzle exit conditions can improve understanding of the atomization mechanisms responsible for pMDI spray droplet and particle formation.

Original languageEnglish
Pages (from-to)1249-1258
Number of pages10
JournalPharmaceutical Research
Volume33
Issue number5
DOIs
Publication statusPublished - 1 May 2016

Keywords

  • pressurised metered dose inhaler
  • radiography
  • synchrotron radiation
  • X-ray

Cite this

Mason-Smith, Nicholas ; Duke, Daniel J. ; Kastengren, Alan L. ; Stewart, Peter J. ; Traini, Daniela ; Young, Paul M. ; Chen, Yang ; Lewis, David A. ; Soria, Julio ; Edgington-Mitchell, Daniel ; Honnery, Damon. / Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography. In: Pharmaceutical Research. 2016 ; Vol. 33, No. 5. pp. 1249-1258.
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abstract = "Purpose: Typical methods to study pMDI sprays employ particle sizing or visible light diagnostics, which suffer in regions of high spray density. X-ray techniques can be applied to pharmaceutical sprays to obtain information unattainable by conventional particle sizing and light-based techniques. Methods: We present a technique for obtaining quantitative measurements of spray density in pMDI sprays. A monochromatic focused X-ray beam was used to perform quantitative radiography measurements in the near-nozzle region and plume of HFA-propelled sprays. Results: Measurements were obtained with a temporal resolution of 0.184 ms and spatial resolution of 5 μm. Steady flow conditions were reached after around 30 ms for the formulations examined with the spray device used. Spray evolution was affected by the inclusion of ethanol in the formulation and unaffected by the inclusion of 0.1{\%} drug by weight. Estimation of the nozzle exit density showed that vapour is likely to dominate the flow leaving the inhaler nozzle during steady flow. Conclusions: Quantitative measurements in pMDI sprays allow the determination of nozzle exit conditions that are difficult to obtain experimentally by other means. Measurements of these nozzle exit conditions can improve understanding of the atomization mechanisms responsible for pMDI spray droplet and particle formation.",
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Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography. / Mason-Smith, Nicholas; Duke, Daniel J.; Kastengren, Alan L.; Stewart, Peter J.; Traini, Daniela; Young, Paul M.; Chen, Yang; Lewis, David A.; Soria, Julio; Edgington-Mitchell, Daniel; Honnery, Damon.

In: Pharmaceutical Research, Vol. 33, No. 5, 01.05.2016, p. 1249-1258.

Research output: Contribution to journalArticleResearchpeer-review

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N2 - Purpose: Typical methods to study pMDI sprays employ particle sizing or visible light diagnostics, which suffer in regions of high spray density. X-ray techniques can be applied to pharmaceutical sprays to obtain information unattainable by conventional particle sizing and light-based techniques. Methods: We present a technique for obtaining quantitative measurements of spray density in pMDI sprays. A monochromatic focused X-ray beam was used to perform quantitative radiography measurements in the near-nozzle region and plume of HFA-propelled sprays. Results: Measurements were obtained with a temporal resolution of 0.184 ms and spatial resolution of 5 μm. Steady flow conditions were reached after around 30 ms for the formulations examined with the spray device used. Spray evolution was affected by the inclusion of ethanol in the formulation and unaffected by the inclusion of 0.1% drug by weight. Estimation of the nozzle exit density showed that vapour is likely to dominate the flow leaving the inhaler nozzle during steady flow. Conclusions: Quantitative measurements in pMDI sprays allow the determination of nozzle exit conditions that are difficult to obtain experimentally by other means. Measurements of these nozzle exit conditions can improve understanding of the atomization mechanisms responsible for pMDI spray droplet and particle formation.

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