Gamma scintigraphic evaluation of a novel budesonide dry powder inhaler using a validated radiolabeling technique.
A scintigraphic study was carried out to compare the lung deposition of budesonide delivered via Clickhaler and Turbuhaler dry powder inhalers in healthy volunteers. Validation of Technetium-99m ((99m)Tc) radiolabeling of the budesonide/lactose blend used in the Clickhaler and excipient-free budesonide used in the Turbuhaler was carried out using a multistage liquid impinger, and compared with reference unlabeled devices. Budesonide was quantified using high-performance liquid chromatography and (99m)Tc by scintillation counting. The percentages (SD) of fine particles (<5.5 microm diameter) from radiolabeled and unlabeled devices were not significantly different (p > 0.05). Mean values for drug and radiolabel, respectively, were 34.6% (2.5) and 31.6% (3.8) for the Clickhaler, and 29.8% (5.5) and 31.4% (5 6) for the Turbuhaler. Fifteen healthy male volunteers received a single dose (2 x 200 microg actuations) from both devices in a double-blinded, double dummy, crossover study. During dosing, each inhalation maneuver was recorded using a computer-linked pressure transducer. To permit accurate determination of radiolabeled drug deposition, the lung margins of each volunteer were determined by Krypton-81m ((81m)Kr) gas imaging. Mean [SD] lung deposition for the Clickhaler (26.8% [6.8], RSD 25.2) was significantly greater (p < 0.001) than for the Turbuhaler (15.8% [6.6], RSD 42.2). Inspiratory flow rate parameters were similar for both devices with peak and mean values of 73 and 51 L/min for the Clickhaler, and 73 and 47 L/min for the Turbuhaler, respectively. These results indicate that, in healthy volunteers, budesonide lung deposition was higher and more consistent with the Clickhaler than with the Turbuhaler.
Warren
Simon
S
Cardiff Scintigraphics Limited, Cardiff, United Kingdom.
Taylor
Glyn
G
Smith
Jeffrey
J
Buck
Helen
H
Parry-Billings
Mark
M
D000328:Adult; D000704:Analysis of Variance; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019819:Budesonide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007727:Krypton Radioisotopes; D008168:Lung / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders; D011877:Radionuclide Imaging; D012588:Scintillation Counting; D013670:Sodium Pertechnetate Tc 99m; D014018:Tissue Distribution
D001993:Bronchodilator Agents; D007727:Krypton Radioisotopes; D011208:Powders; D019819:Budesonide; D013670:Sodium Pertechnetate Tc 99m