Article

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: 2.89). 02/2010; 23(1):41-6. DOI: 10.1089/jamp.2008.0740
Source: PubMed

ABSTRACT 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.

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