Dry powder aerosols generated by standardized entrainment tubes from drug blends with lactose monohydrate: 1. Albuterol sulfate and disodium cromoglycate

J Pharm Sci. 2010 Aug;99(8):3398-414. doi: 10.1002/jps.22107.

Abstract

The major objective of this study was: discriminatory assessment of dry powder aerosol performance using standardized entrainment tubes (SETs) and lactose-based formulations with two model drugs. Drug/lactose interactive physical mixtures (2%w/w) were prepared. Their properties were measured: solid-state characterization of phase behavior and molecular interactions by differential scanning calorimetry and X-ray powder diffraction; particle morphology and size by scanning electron microscopy and laser diffraction; aerosol generation by SETs and characterization by twin-stage liquid impinger and Andersen cascade impactor operated at 60 L/min. The fine particle fraction (FPF) was correlated with SET shear stress (tau(s)), using a novel powder aerosol deaggregation equation (PADE). Drug particles were <5 microm in volume diameter with narrow unimodal distribution (Span <1). The lowest shear SET (tau(s) = 0.624 N/m(2)) gave a higher emitted dose (ED approximately 84-93%) and lower FPF (FPF(6.4) approximately 7-25%). In contrast, the highest shear SET (tau(s) = 13.143 N/m(2)) gave a lower ED (ED approximately 75-89%) and higher FPF (FPF(6.4) approximately 15-46%). The performance of disodium cromoglycate was superior to albuterol sulfate at given tau(s), as was milled with respect to sieved lactose monohydrate. Excellent correlation was observed (R(2) approximately 0.9804-0.9998) when pulmonary drug particle release from the surface of lactose carriers was interpreted by PADE linear regression for dry powder formulation evaluation and performance prediction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Aerosols
  • Albuterol / administration & dosage
  • Albuterol / chemistry*
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / chemistry*
  • Calorimetry, Differential Scanning
  • Chemistry, Pharmaceutical
  • Cromolyn Sodium / administration & dosage
  • Cromolyn Sodium / chemistry*
  • Crystallization
  • Drug Carriers
  • Drug Compounding / instrumentation
  • Lactose / chemistry*
  • Lasers
  • Microscopy, Electron, Scanning
  • Particle Size
  • Powders
  • Thermodynamics
  • X-Ray Diffraction

Substances

  • Aerosols
  • Anti-Asthmatic Agents
  • Drug Carriers
  • Powders
  • Lactose
  • Cromolyn Sodium
  • Albuterol