CONTROLLED-RELEASE FROM CONDENSATION COATED RESPIRABLE AEROSOL-PARTICLES

Extending the residence time of drugs delivered to the lungs as inhala tion aerosols may result in sustained therapeutic drug levels and redu ced toxicity. Droplets were generated from 0.25 wt% disodium fluoresce in (DF), and 0.25 wt% albuterol sulphate solutions at a rate of 1 ml m in-1 using a Turbotac jet nebulizer. These droplets were dried, concen trated and mixed with saturated lauric acid (LA) vapor at bath tempera tures of 60-140-degrees-C. The resulting coated particles were < 5 mum in size as estimated by inertial impaction and scanning electron micr oscopy. Powder composition, as determined by gas chromatography, range d 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. Diss olution studies performed on the coated particles in phosphate buffer, pH 7.4 at 37-degrees-C and quantified by u.v. spectroscopy, showed th at the half-time for dissolution (t1.2) increased from 4 +/- 2 min for uncoated DF particles, to 22 +/- 3-55 +/- 2 min for lauric acid coate d DF particles, depending on the coating thickness. The t1/2 for albut erol 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 bat h temperature of 100-degrees-C. Inhalation studies performed on beagle dogs with DF particles coated with lauric acid (bath temperature, 100 -degrees-C) indicated there was a shift and broadening of the peak pla sma concentration in comparison with aerosols of DF alone. The average absorption half-time increased from 4.7 +/- 0.8 min for uncoated DF p articles to 11.5 +/- 1.6 min for lauric acid coated DF particles.