Measurement of the Raman spectra and hygroscopicity of four pharmaceutical aerosols as they travel from pressurised metered dose inhalers (pMDI) to a model lung.
Particle inhalation is an effective and rapid delivery method for a variety of pharmaceuticals, particularly bronchodilation drugs used for treating asthma and COPD. Conditions of relative humidity and temperature inside the lungs are generally very different from the outside ambient air, with the lung typically being warmer and more humid. Changes in humidity, from inhaler to lung, can cause hygroscopic phase transitions and particle growth. Increasing particle size and mass can negatively affect particle deposition within the lung leading to inefficient treatment, while deliquescence prior to impaction is liable to accelerate drug uptake. To better understand the hygroscopic properties of four pharmaceutical aerosol particles; pharmaceutical particles from four commercially available pressurised metered dose inhalers (pMDIs) were stably captured in an optical trap, and their composition was examined online via Raman spectroscopy. Micron-sized particles of salbutamol sulfate, salmeterol xinafoate, fluticasone propionate and ciclesonide were levitated and examined over a range of relative humidity values inside a chamber designed to mimic conditions within the respiratory tract. The effect of temperature upon hygroscopicity was also investigated for salbutamol sulfate particles. Salbutamol sulfate was found to have significant hygroscopicity, salmeterol xinafoate showed some hygroscopic interactions, whilst fluticasone propionate and ciclesonide revealed no observable hygroscopicity. Thermodynamic and structural modelling is used to explain the observed experimental results.
School of Geography, Earth and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
N
N
Davidson
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
H-J
HJ
Tong
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
M
M
Kalberer
School of Pharmacy, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancs, PR1 2HE, UK.
P C
PC
Seville
Central Laser Facility, Rutherford Appleton Laboratory, Harwell, Oxford, OX11 0QX, UK.
A D
AD
Ward
Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
M K
MK
Kuimova
School of Geography, Earth and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. Electronic address: f.pope@bham.ac.uk.
F D
FD
Pope
D000336:Aerosols / Q000737:chemistry*; D000420:Albuterol / Q000737:chemistry; D000068298:Fluticasone / Q000737:chemistry; D006813:Humidity; D036501:Metered Dose Inhalers; D008961:Models, Structural; D010316:Particle Size; D011282:Pregnenediones / Q000737:chemistry; D000068299:Salmeterol Xinafoate / Q000737:chemistry; D013059:Spectrum Analysis, Raman; D013696:Temperature; D017155:Wettability
D000336:Aerosols; D011282:Pregnenediones; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol; C120481:ciclesonide
Ciclesonide (PubChem CID: 6918155); Fluticasone propionate (PubChem CID: 444036); Hygroscopicity; Laser tweezers; Optical trapping; Salbutamol sulfate (PubChem CID: 39859); Salmeterol xinafoate (PubChem CID: 56801); Suspended particle; pMDI