Measurement of the Raman spectra and hygroscopicity of four pharmaceutical aerosols as they travel from pressurised metered dose inhalers (pMDI) to a model lung

Abstract

Measurement of the Raman spectra and hygroscopicity of four pharmaceutical aerosols as they travel from pressurised metered dose inhalers (pMDI) to a model lung.International Journal of Pharmaceutics http://dx

1064 nm Dispersive Raman Microspectroscopy and Optical Trapping of Pharmaceutical Aerosols

“…Spectra obtained for all three pharmaceutical aerosols compare very well with previous literature and theoretical predictions 10,11,22,23 . Major features for salmeterol xinafoate include ring stretches (1000, 1022, 1582 and 1620 cm -1 ), an amine stretch (1204 cm -1 ), a C-O bending mode (1369 cm -1 ) and C-H bending modes (1432 and 1467 cm -1 ).…”

“…b) shows spectra for the asthma drug salmeterol xinafoate, acquired following different exposure times to a 514.5 nm excitation laser. The spectrum initially resembles previous spectra reported in the literature10 , but as noted in Davidson et al11 , fluorescence commences almost immediately following irradiation by the visible laser due to the presence of the fluorophore in xinafoic acid. Since one of the key advantages of optical trapping techniques is the ability to interrogate single particles over long periods of time, photochemical sample degradation represents a major limitation for samples containing organic fluorophores.…”

“…Particles were introduced into an environmental chamber for analysis. The chamber design has been reported previously 11,17 . It consists of an aluminium cell with internal dimensions 10 × 2 × 1 cm, with borosilicate glass windows at the top and bottom to transmit the optical trapping and Raman laser beams (described in section 2.2).…”

“…Pressurised Metered Dose Inhalers (pMDIs) are an effective and rapid means of delivering pharmaceuticals to the lungs, and are the most commonly used delivery system for treating asthma, chronic obstructive pulmonary disease and other respiratory diseases 9 . Raman spectroscopy enables polymorphic crystal forms of drugs to be distinguished 10 , and the uptake of water vapour to be monitored on the particle's journey from inhaler to a high humidity "model lung" 11 .…”

A review of experimental techniques for aerosol hygroscopicity studies

“…Hygroscopicity is related to the possible existence of liquid water in some hyperarid environments (such as Mars and the Atacama Desert on Earth) (Martin-Torres et al, 2015): while pure liquid water is not stable in these environments, the deliquescence of some salts, such as chlorides and perchlorates, can occur at RH significantly below 100 % and lead to the formation of aqueous solutions (Gough et al, 2011(Gough et al, , 2016Gu et al, 2017a;Jia et al, 2018). Hygroscopic properties significantly affect transport and deposition of inhaled aerosol particles in the respiratory tract, therefore playing an important role in the health impact of ambient aerosols as well as efficacy and side effects of aerosolized pharmaceuticals (Hickey and Martonen, 1993;Robinson and Yu, 1998;Carvalho et al, 2011;Hofmann, 2011;Haddrell et al, 2014;Winkler-Heil et al, 2014, 2017Darquenne et al, 2016;Davidson et al, 2017). Impacts of moisture and implications of hygroscopicity have been well documented for physical and chemical stability of pharmaceuticals (Ahlneck and Zografi, 1990;Chan et al, 1997;Peng et al, 2000;Newman et al, 2008;Mauer and Taylor, 2010a;Tong et al, 2010a;Feth et al, 2011) as well as food ingredients and blends (Mauer and Taylor, 2010b;Allan and Mauer, 2016), and large efforts have been made in the pharmaceutical and food industries to prevent relevant products from deliquescence.…”