Effect of particle size of dry powder mannitol on the lung deposition in healthy volunteers.
There is a lack of in vivo studies focusing on the effect of particle size of dry powder aerosols on lung deposition and distribution. We investigated the dose and distribution of radiolabelled powder aerosols of mannitol in the lungs using single photon emission tomography (SPECT). Three different sized radiolabelled powders were produced by co-spray drying mannitol with 99mTc-DTPA. The primary particle size distribution of the powders measured by laser diffraction showed a volume median diameter of 2, 3 and 4 microm with span 2.3, 2.0 and 2.1, respectively, which corresponded to an aerodynamic diameter of 2.7, 3.6, 5.4 microm and geometric standard deviation of 2.6, 2.4 and 2.7 when the powders were dispersed using an Aeroliser dry powder inhaler. Three capsules each containing approximately 20mg (i.e. a total of 60 mg containing 60-90 MBq) of each of the radiolabelled powders were inhaled by eight healthy volunteers using the Aeroliser inhaler. Images of aerosol deposition in the lungs were acquired using fast, multi-bed position SPECT. The lung dose markedly decreased with increasing aerosol particle size (mean+/-S.E.M.: 44.8+/-2.4, 38.9+/-0.9, 20.6+/-1.6% for 2.7, 3.6, 5.4 microm, respectively, p<0.0001). The sites of deposition of the 2.7 and 3.6 microm aerosols were similar (penetration index, PI=0.63+/-0.05, 0.60+/-0.03, respectively, p>0.3), but different to the 5.4 microm aerosols (PI=0.52+/-0.04, p<0.02). The lung dose followed the in vitro powder dispersion performance, with the % lung dose being related to fine particle fraction by a slope of 0.8 for a regression with intercepts forced through the origin. The SPECT results provide direct evidence that the lung deposition of dry powder aerosols depends on the particle size. The lung dose of the 2.7 and 3.6 microm aerosols using the Aeroliser was double compared to that of the 5.4 microm aerosols and the deposition of the smaller particles was more peripheral.
Glover
William
W
Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, NSW 2006, Australia.
Chan
Hak-Kim
HK
Eberl
Stefan
S
Daviskas
Evangelia
E
Verschuer
Jordan
J
D000280:Administration, Inhalation; D000328:Adult; D003627:Data Interpretation, Statistical; D003890:Desiccation; D004339:Drug Compounding; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007553:Isotope Labeling; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010316:Particle Size; D011208:Powders; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon
D011208:Powders; D019275:Radiopharmaceuticals; D008353:Mannitol; D016284:Technetium Tc 99m Pentetate