A R Brown1, D W George. 1. Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan 66506, USA. Brown@vet.ksu.edu
Abstract
PURPOSE: Develop metered-dose propellant-driven aerosols of proteins using tetrafluoroethane (HFC 134A) as propellant. METHODS: Proteins were lyophilized with the propellant-soluble surfactants Triton X-100, Triton X-405, Laureth-9, Brij-30, Nonidet-40, and diethylene glycol monoethylether and then charged with propellants. RESULTS: Small particle aerosols of the experimental protein bovine gamma globulin were produced. The fraction of aerosolized respirable-sized protein particles (< 4-5 microns) increased after dispersion of particles in propellant with agitation by shaking. Scanning electron microscopy of respirable-sized protein aerosols demonstrated bead-like particles in grape-like clusters. Vigorous shaking of propellant-suspended particles for 2 minutes or more reduced the size of clusters and reduced the diameters of the protein-containing subparticles that constituted the clusters. A 50:50 ratio of HFC 134A and dimethylether (DME) propellants improved the respirability of protein aerosols compared to HFC 134A as the sole propellant. Protein/surfactant particles first dispersed in DME and then diluted in HFC 134A propellant most efficiently produced respirable-sized, propellant-driven, protein aerosols.
PURPOSE: Develop metered-dose propellant-driven aerosols of proteins using tetrafluoroethane (HFC 134A) as propellant. METHODS: Proteins were lyophilized with the propellant-soluble surfactants Triton X-100, Triton X-405, Laureth-9, Brij-30, Nonidet-40, and diethylene glycol monoethylether and then charged with propellants. RESULTS: Small particle aerosols of the experimental protein bovine gamma globulin were produced. The fraction of aerosolized respirable-sized protein particles (< 4-5 microns) increased after dispersion of particles in propellant with agitation by shaking. Scanning electron microscopy of respirable-sized protein aerosols demonstrated bead-like particles in grape-like clusters. Vigorous shaking of propellant-suspended particles for 2 minutes or more reduced the size of clusters and reduced the diameters of the protein-containing subparticles that constituted the clusters. A 50:50 ratio of HFC 134A and dimethylether (DME) propellants improved the respirability of protein aerosols compared to HFC 134A as the sole propellant. Protein/surfactant particles first dispersed in DME and then diluted in HFC 134A propellant most efficiently produced respirable-sized, propellant-driven, protein aerosols.
Authors: P Chervinsky; A van As; E A Bronsky; R Dockhorn; M Noonan; C LaForce; W Pleskow Journal: J Allergy Clin Immunol Date: 1994-10 Impact factor: 10.793