Improved lung delivery from a passive dry powder inhaler using an Engineered PulmoSphere powder |
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Authors: | Duddu Sarma P Sisk Steven A Walter Yulia H Tarara Thomas E Trimble Kevin R Clark Andrew R Eldon Michael A Elton Rebecca C Pickford Matthew Hirst Peter H Newman Stephen P Weers Jeffry G |
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Institution: | (1) Inhale Therapeutic Systems Inc, San Carlos, California, 94070;(2) Pharmaceutical Profiles Ltd, Nottingham, United Kingdom |
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Abstract: | Purpose. 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 g budesonide PulmoSphere inhaled from Eclipse® DPI at target PIF of 25 L·min-1 (PSbud25), and 50 L·min-1 (PSbud50), and 800 g of pelletized budesonide from Pulmicort® Turbuhaler® at 60 L·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·min-1, respectively. Mean peak plasma budesonide levels were 4.7 (PSbud25), 4.0 (PSbud50), and 2.2 ng·ml-1 (THbud60). Median tmax 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·h·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·min-1 from the Turbuhaler. Intersubject variability was also dramatically decreased for PSbud relative to THbud.
Conclusion. Delivery of an engineered PulmoSphere formulation is more efficient and reproducible than delivery of micronized drug from passive DPIs. |
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Keywords: | pulmonary drug delivery dry powder inhaler particle engineering spray-drying pharmacoscintigraphy Eclipse® |
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