title: An in vivo and in vitro comparison of two powder inhalers following storage at hot/humid conditions.
abstract: Dry powder inhalers (DPIs) are increasingly being used for the treatment of asthma and COPD. A potential drawback is that DPIs can be sensitive to humidity. Two DPIs, Symbicort Turbuhaler and Seretide Diskus, were stored 3 months at either 25 degrees C/30% RH or 40 degrees C/75% RH. After storage, delivered, as well as fine particle dose, FPD, were tested in vitro and lung deposition, of the steroid components, was assessed in vivo. After storage at 40 degrees C/75% RH, delivered dose as well as FPD from Symbicort Turbuhaler was virtually unchanged while FPD for Seretide Diskus decreased by about 50% despite no decrease in delivered dose. For both products, no difference in FPD was seen after storage at 25 degrees C/30% RH. These in vitro findings were confirmed in the in vivo part of the study. Lung deposition for Symbicort Turbuhaler was unaffected by 40 degrees C/75% RH storage, while for Seretide Diskus it was reduced with about 50%. The study extends previous in vitro observations of impaired performance of Seretide Diskus and demonstrates that this translates into decreased drug delivery to the site of action. The clinical importance of this finding has not been studied but could result in undertreatment.
authors.affiliation: AstraZeneca R and D, Lund, Sweden. Lars.borgstrom@astrazeneca.com
authors.forename: Lars
authors.initials: L
authors.lastname: Borgström
authors.forename: Lars
authors.initials: L
authors.lastname: Asking
authors.forename: Peter
authors.initials: P
authors.lastname: Lipniunas
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000730:Androstadienes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019819:Budesonide / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000069502:Budesonide, Formoterol Fumarate Drug Combination; D018592:Cross-Over Studies; D004338:Drug Combinations; D004356:Drug Storage; D004983:Ethanolamines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D006358:Hot Temperature; D006801:Humans; D006813:Humidity; D008168:Lung / Q000378:metabolism; D008297:Male; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D001993:Bronchodilator Agents; D000069502:Budesonide, Formoterol Fumarate Drug Combination; D004338:Drug Combinations; D004983:Ethanolamines; D000068297:Fluticasone-Salmeterol Drug Combination; D011208:Powders; D019819:Budesonide; D000420:Albuterol