Improved lung delivery from a passive dry powder inhaler using an engineered PulmoSphere® powder

• Published in: Pharmaceutical research Vol. 19; no. 5; pp. 689 - 695
• Main Authors: DUDDU, Sarma P, SISK, Steven A, NEWMAN, Stephen P, WEERS, Jeffry G, WALTER, Yulia H, TARARA, Thomas E, TRIMBLE, Kevin R, CLARK, Andrew R, ELDON, Michael A, ELTON, Rebecca C, PICKFORD, Matthew, HIRST, Peter H
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01.05.2002; Springer Nature B.V
• Subjects: Administration, Inhalation; Adult; Biological and medical sciences; Budesonide - administration & dosage; Budesonide - pharmacokinetics; Cross-Over Studies; Female; Gas Chromatography-Mass Spectrometry; General pharmacology; Humans; Isotope Labeling; Lung - metabolism; Male; Medical sciences; Metered Dose Inhalers; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Powders; Radioisotopes; Reproducibility of Results; Respiratory system; Technetium; Tissue Distribution; Human; Delivery system; Budesonide; Corticosteroid; Pharmaceutical technology; Healthy subject; Toxicity; Lung; Antiinflammatory agent; Intrapulmonary administration; Respiratory system; Powder; Blood; Blood plasma; Registered trade mark; Inhaler; Commercial form; Pharmacokinetics; Deposition
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1015322616613

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). 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. 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. Delivery of an engineered PulmoSphere formulation is more efficient and reproducible than delivery of micronized drug from passive DPIs.