Improved lung delivery from a passive dry powder inhaler using an Engineered PulmoSphere powder.
OBJECTIVE
To assess the pulmonary deposition and pharmacokinetics of an engineered PulmoSphere powder relative to standard micronized drug when delivered from passive dry powder inhalers (DPIs).


METHODS
Budesonide PulmoSphere (PSbud) powder was manufactured using an emulsion-based spray-drying process. Eight healthy subjects completed 3 treatments in crossover fashion: 370 microg budesonide PulmoSphere inhaled from Eclipse DPI at target PIF of 25 L x min(-1) (PSbud25), and 50 L x min(-1) (PSbud50), and 800 microg of pelletized budesonide from Pulmicort Turbuhaler at 60 L x min(-1)(THbud60). PSbud powder was radiolabeled with 99mTc and lung deposition determined scintigraphically. Plasma budesonide concentrations were measured for 12 h after inhalation.


RESULTS
Pulmonary deposition (mean +/- sd) of PSbud was 57+/-7% and 58+/-8% of the nominal dose at 25 and 50 L x min(-1), respectively. Mean peak plasma budesonide levels were 4.7 (PSbud25), 4.0 (PSbud50), and 2.2 ng x ml(-1) (THbud60). Median t(max) was 5 min after both PSbud inhalations compared to 20 min for Turbuhaler (P < 0.05). Mean AUCs were comparable after all inhalations, 5.1 (PSbud25), 5.9 (PSbud50), and 6.0 (THbud60) ng x h x ml(-1). The engineered PSbud powder delivered at both flow rates from the Eclipse DPI was twice as efficiently deposited as pelletized budesonide delivered at 60 L x min(-1) from the Turbuhaler. Intersubject variability was also dramatically decreased for PSbud relative to THbud.


CONCLUSIONS
Delivery of an engineered PulmoSphere formulation is more efficient and reproducible than delivery of micronized drug from passive DPIs.
Duddu
Sarma P
SP
Inhale Therapeutic Systems Inc., San Carlos, California 94070, USA.
Sisk
Steven A
SA
Walter
Yulia H
YH
Tarara
Thomas E
TE
Trimble
Kevin R
KR
Clark
Andrew R
AR
Eldon
Michael A
MA
Elton
Rebecca C
RC
Pickford
Matthew
M
Hirst
Peter H
PH
Newman
Stephen P
SP
Weers
Jeffry G
JG
D000280:Administration, Inhalation; D000328:Adult; D019819:Budesonide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007553:Isotope Labeling; D008168:Lung / Q000378:metabolism; D008297:Male; D036501:Metered Dose Inhalers; D010316:Particle Size; D011208:Powders; D011868:Radioisotopes; D015203:Reproducibility of Results; D013667:Technetium; D014018:Tissue Distribution
D011208:Powders; D011868:Radioisotopes; D019819:Budesonide; D013667:Technetium