Controlled release from condensation coated respirable aerosol particles

Abstract

Extending the residence time of drugs delivered to the lungs as inhalation aerosols may result in sustained therapeutic drug levels and reduced toxicity. Droplets were generated from 0.25 wt% disodium fluorescein (DF), and 0.25 wt% albuterol sulphate solutions at a rate of 1 ml min −1 using a Turbotac jet nebulizer. These droplets were dried, concentrated and mixed with saturated lauric acid (LA) vapor at bath temperatures of 60–140°C. The resulting coated particles were < 5 μm in size as estimated by inertial impaction and scanning electron microscopy. Powder composition, as determined by gas chromatography, ranged from ratios of 1.2:1 to 2.5:1, of LA: DF. Evidence of coating of DF by LA was derived from i.r. spectroscopy and X-ray microanalysis. Dissolution studies performed on the coated particles in phosphate buffer, pH 7.4 at 37°C and quantified by u.v. spectroscopy, showed that the half-time for dissolution ( t 2) increased from 4 ± 2 min for uncoated DF particles, to 22 ± 3 − 55 ± 2 min for lauric acid coated DF particles, depending on the coating thickness. The t 1 2 for albuterol sulphate particles increased from 2.5 ± 1.5 min to 12.5 ± 1.9 min for albuterol sulphate particles coated with lauric acid at a bath temperature of 100°C. Inhalation studies performed on beagle dogs with DF particles coated with lauric acid (bath temperature, 100°C) indicated there was a shift and broadening of the peak plasma concentration in comparison with aerosols of DF alone. The average absorption half-time increased from 4.7 ± 0.8 min for uncoated DF particles to 11.5 ± 1.6 min for lauric acid coated DF particles.