Evaluation of Lung Tolerance of Ethanol, Propylene Glycol, and Sorbitan Monooleate as Solvents in Medical Aerosols

INSERM U618, IFR135, Faculté de Médecine, CHRU Bretonneau, Tours, France.
Journal of Aerosol Medicine and Pulmonary Drug Delivery (Impact Factor: 2.8). 02/2010; 23(1):41-6. DOI: 10.1089/jamp.2008.0740
Source: PubMed


Aerosol therapy is an expanding technique allowing administration of drugs acting locally in the bronchial tree and lungs or acting systemically after absorption through the respiratory tract. However, the choice of solvents and adjuvants is a critical step in the formulation process of new drugs. Pulmonary tolerance of ethanol, propylene glycol and sorbitan ester was evaluated in a rat model of intratracheal administration using a Microsprayer in a 4-day toxicity study.
Four groups of Sprague-Dawley rats (11 rats per group, n = 44) have received, on 4 consecutive days 150 microL of solutions containing the solvents, by intratracheal route using a IA-1B-2 inches-Microsprayer (PennCentury, Philadelphia, PA). Once a day, the rats received deionized water (control) or ethanol 10% or propylene glycol 30% or sorbitan monooleate 10%. All rats were sacrificed 24 h after the fourth administration. Biochemical analysis on bronchoalveolar lavage (BAL) fluid was performed on seven rats per group. The respiratory tract of the remaining four rats/group was examined histologically.
Biochemistry and histopathology findings demonstrated that under the conditions tested, deionized water, 10% ethanol, and 30% propylene glycol were tolerated in a qualitatively similar way presenting limited cellular reaction. In contrast, 10% sorbitan monooleate produced an accumulation of foamy macrophages in the lungs and a higher degree of inflammation. In addition, animals in this group showed higher polymorphonuclear neutrophil recruitment and total proteins levels in BAL fluid.
The overall results recommended ranking the vehicles according to the degree of inflammation which was induced: deionized water <10% ethanol < or =30% propylene glycol <10% Tween 80.

Download full-text


Available from: Patrice Diot, Jan 11, 2016
  • Source
    • "of 10 9 particles / cm 3 . After dilution very small particle diameters in the range of 50 nm were observed , which probably resulted from almost complete evaporation of the e - cigarette aerosol particles . 1 , 2 - Propanediol is not acutely toxic and there is also no evidence of genotoxic or carcinogenic action of 1 , 2 - propanediol in humans ( Montharu et al . , 2010 ; Werley et al . , 2011 ) . However , it cannot be deduced from this , that long - term inhalation of fine and ultrafine 1 , 2 - propanediol droplets must be completely safe . Such particles are assumed to be deposited in the deeper parts of the lung and may cause respiratory irritations ( Wieslander et al . , 2001 ) or can increase the"
    [Show abstract] [Hide abstract]
    ABSTRACT: Waterpipe (WP) smoking is growing as an alternative to cigarette smoking, especially in younger age groups. E-cigarette use has also increased in recent years. A majority of smokers mistakenly believe that WP smoking is a social entertainment practice that leads to more social behavior and relaxation and that this type of smoking is safe or less harmful and less addictive than cigarette smoking. In reality, WP smokers are exposed to hundreds of toxic substances that include known carcinogens. High exposures to carbon monoxide and nicotine are major health threats. Persons exposed to secondhand WP smoke are also at risk. There is growing evidence that WP smoke causes adverse effects on the pulmonary and cardiovascular systems and is responsible for cancer.
    Full-text · Article · Apr 2015 · Atmospheric Environment
  • Source
    • "A common carrier of the ÔliquidsÕ is 1,2-propanediol (propylene glycol, PG) that leads to a visible fume during exhalation. This compound is also frequently used as a solvent in dosage formulations of aerosolized drug delivery systems such as pressurized metered-dose inhalers and nebulizers for the clinical practice (Montharu et al., 2010). However, the frequency of use is expected to be higher in case of e-cigarette vaping, leading to a different exposure pattern. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Unlabelled: Electronic cigarette consumption ('vaping') is marketed as an alternative to conventional tobacco smoking. Technically, a mixture of chemicals containing carrier liquids, flavors, and optionally nicotine is vaporized and inhaled. The present study aims at the determination of the release of volatile organic compounds (VOC) and (ultra)fine particles (FP/UFP) from an e-cigarette under near-to-real-use conditions in an 8-m(3) emission test chamber. Furthermore, the inhaled mixture is analyzed in small chambers. An increase in FP/UFP and VOC could be determined after the use of the e-cigarette. Prominent components in the gas-phase are 1,2-propanediol, 1,2,3-propanetriol, diacetin, flavorings, and traces of nicotine. As a consequence, 'passive vaping' must be expected from the consumption of e-cigarettes. Furthermore, the inhaled aerosol undergoes changes in the human lung that is assumed to be attributed to deposition and evaporation. Practical implications: The consumption of e-cigarettes marks a new source for chemical and aerosol exposure in the indoor environment. To evaluate the impact of e-cigarettes on indoor air quality and to estimate the possible effect of passive vaping, information about the chemical characteristics of the released vapor is needed.
    Preview · Article · Jun 2012 · Indoor Air
  • [Show abstract] [Hide abstract]
    ABSTRACT: The project for a European standard testing procedure to characterize nebulizers in terms of particle size distribution has been based on using the Andersen-Marple personal cascade impactor model 298 (A-MPCI) with a sodium fluoride reference solution. In the present study methods based on laser diffraction (Mastersizer-X) and time-of-flight (TOF)(APS) and another cascade impactor (GS1-CI) were compared with the A-MPCI. Two types of nebulizer (Pari LC+ and Microneb) were tested with all apparatuses, and a third type of nebulizer (NL9) was tested with the A-MPCI and Mastersizer-X. Nebulizers were charged with a solution of sodium fluoride in conditions reproducing the European Committee for Normalization (CEN) protocol. There was no difference between the Mastersizer-X and the A-MPCI or between the GS1-CI and the A-MPCI in terms of mass median aerodynamic diameter (MMAD). Comparison between the APS and the A-MPCI showed a significant difference with the Microneb. The geometric standard deviations (GSD) obtained with the A-MPCI were on average 10% greater than GSD obtained with the other apparatuses, but the differences were not statistically significant. We conclude that laser diffraction can be used for particle size distribution in the context of the European standard, and that the Mastersizer-X is particularly interesting for industrial practice in view of its simplicity and robustness.
    No preview · Article · Feb 2001 · Journal of Aerosol Medicine
Show more