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Keywords:

  • aerosols;
  • dry powder inhaler;
  • pulmonary drug delivery;
  • physical characterization;
  • standardized entrainment tubes;
  • shear stress;
  • emitted dose;
  • fine particle fraction;
  • aerosolization performance;
  • powder aerosol deaggregation equation

Abstract

The objectives of this study were: systematic investigation of dry powder aerosol performance using standardized entrainment tubes (SETs) and lactose-based formulations with two model drugs; mechanistic evaluation of performance data by powder aerosol deaggregation equation (PADE). The drugs (IPB and FP) were prepared in sieved and milled lactose carriers (2% w/w). Aerosol studies were performed using SETs (shear stresses τs = 0.624–13.143 N/m2) by twin-stage liquid impinger, operated at 60 L/min. PADE was applied for formulation screening. Excellent correlation was observed when PADE was adopted correlating FPF to τs. Higher τs corresponded to higher FPF values followed by a plateau representing invariance of FPF with increasing τs. The R2 values for PADE linear regression were 0.9905–0.9999. Performance described in terms of the maximum FPF (FPFmax: 15.0–37.6%) resulted in a rank order of ML-B/IPB > ML-A/IPB > SV-A/IPB > SV-B/IPB > ML-B/FP > ML-A/FP > SV-B/FP > SV-A/FP. The performance of IPB was superior to FP in all formulations. The difference in lactose monohydrate carriers was less pronounced for the FPF in IPB than in FP formulations. The novel PADE offers a robust method for evaluating aerodynamic performance of dry powder formulations within a defined τs range. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3415–3429, 2010