The influence of drug loading on formulation structure and aerosol performance in carrier based dry powder inhalers

Paul M. Young, Owen Wood, Jesslynn Ooi, Daniela Traini

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Previous studies have reported that carrier:drug ratio and carrier size influence the aerosol performance of dry powder inhalation systems. These previous studies were complicated by the heterogeneous nature of the carriers used, making it difficult to define an explicit relationship between parameters and performance. Here, the authors studied the influence of drug loading and carrier size on drug aerosol performance using homogeneous spherical model carriers. Different formulations containing drug (salbutamol sulphate) and carriers (polystyrene beads with median diameters of 82.8 μm, 277.5 μm and 582.9 μm, respectively) were prepared by varying the ratio of carrier to drug (from ∼5:1 to ∼85:1). The surface morphology of the carrier particles and force of adhesion were investigated using atomic force microscopy, while the aerosol performance was evaluated using a multi-stage liquid impinger. The carrier surface morphology for all carrier sizes was homogenous with root-mean square roughness values ≤112 nm. No significant difference in the force of adhesion between salbutamol sulphate and the three carrier sizes was observed. Significant differences in aerosol performance of salbutamol sulphate (measured as fine particle dose (FPD) and fraction (FPF) ≤ 5 μm) from the carriers were observed. Specifically, as carrier size increased FPF decreased. In comparison, as drug loading increased there was no change in FPF until a critical threshold was exceeded. Such observations suggest that: (A) aerosolisation performance is governed by carrier collisions and (B) when homogeneous carriers are used, the aerosol performance remains constant with respect to drug concentration, until the formulation transitions from an ordered mix to an agglomerated and/or segregated powder bed.
Original languageEnglish
Pages (from-to)129-135
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume416
Issue number1
DOIs
Publication statusPublished - 15 Sept 2011
Externally publishedYes

Keywords

  • Active sites
  • Dry powder inhaler
  • Spherical carrier
  • Inhalation medicine
  • Powder blending

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