Measurement of the physico-chemical properties of pharmaceutical aerosols as they travel from pressurised metered dose inhalers (pMDI) to a model lung

N. Davidson, H. -J. Tong, M. Kalberer, P. C. Seville, A. Ward, M. Kuimova, F. D. Pope

Four different asthma medications were delivered from pressurised metered dose inhalers (pMDI) to a chamber acting as an artificial lung, where they were captured in a counter-propagating dual beam optical trap. This setup allowed individual drug particles to be levitated in air whilst simultaneously probing the composition of the particle using Raman spectroscopy. The relative humidity (RH) conditions within the chamber were altered to mimic the RH conditions encountered by the pMDI particles as they travel from pMDI release in ambient air to the near saturated RH conditions of inside the lungs. Analysis of the resulting Raman spectra allowed direct observation of the drugs’ hygroscopic properties, determining whether the particles collect water at high RH and thus change their aerodynamic diameter, altering their deposition within the respiratory tract.
Two beta-2 agonists, salbutamol sulfate and salmeterol xinafoate, and two steroids, ciclesonide and fluticasone propionate, were analysed in this manner. At greater than 95% RH, Salbutamol exhibited peak broadening around the polar functional groups in its Raman spectrum, as previously reported (1). This was interpreted as an indication that the trapped drug particle was collecting water from the air, and images of the particle collected at low and high RH with a charge coupled device (CCD) camera showed a clear increase in particle diameter. This work demonstrates the effectiveness of optical trapping for capturing pharmaceutical aerosols for analysis in more representative conditions than a cover slip, and the usefulness of Raman spectroscopy in monitoring the effects of changing external conditions such as RH and temperature.

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