Inhalation performance of physically mixed dry powders evaluated with a simple simulator for human inspiratory flow patterns

Pharm Res. 2010 Oct;27(10):2131-40. doi: 10.1007/s11095-010-0215-6. Epub 2010 Jul 14.

Abstract

Purpose: To construct a simple simulator reproducing human inspiratory flow patterns and use it to evaluate the inhalation performance of active ingredient particle-carrier particle systems (physically mixed dry powders).

Methods: Inspiratory flow patterns were collected and analyzed using a flow recorder. The simulator was constructed using an airtight container, a valve, and a connecting tube. Several of the patterns reproduced by the simulator were compared with those recorded. In addition, the influence of inspiratory flow on the inhalation performance of physically mixed dry powders composed of salbutamol sulfate (SS) and coarse lactose monohydrate was investigated using a twin-stage liquid impinger (TSLI) equipped with the simulator.

Results: Human inspiratory flow patterns could be characterized by three parameters: inspiratory flow volume (area under the flow rate-time curve (AUC)), flow increase rate (FIR), and peak flow rate (PFR). The patterns could be reproduced using the simulator. Testing with the simulator in vitro revealed that PFR, but not FIR or AUC, greatly affected the inhalation performance of physically mixed dry powders.

Conclusions: The simulator is simple to construct and can schematically reproduce human inspiratory flow patterns. Testing with a TSLI and the simulator is useful to evaluate dry powder formulations for clinical application.

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / administration & dosage*
  • Adrenergic beta-2 Receptor Agonists / chemistry
  • Adrenergic beta-2 Receptor Agonists / pharmacokinetics*
  • Albuterol / administration & dosage*
  • Albuterol / chemistry
  • Albuterol / pharmacokinetics*
  • Chromatography, High Pressure Liquid
  • Dry Powder Inhalers*
  • Humans
  • Lactose / chemistry
  • Microscopy, Electron, Scanning
  • Models, Biological*
  • Powders
  • Surface Properties

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Powders
  • Lactose
  • Albuterol