Tribo-Charging Behaviour of Inhalable Mannitol Blends with Salbutamol Sulphate

Pharm Res. 2019 Apr 9;36(6):80. doi: 10.1007/s11095-019-2612-9.

Abstract

Purpose: The performance of carrier-based dry powder inhaler (DPI) formulations can be critically impacted by interfacial interactions driven by tribo-electrification. Therefore, the aim of the present work was to understand how distinct API particle characteristics affect the charging behaviour of blends intended for DPI delivery.

Methods: Salbutamol sulphate (SBS) particles engineered via spray-drying and jet milling were used as model APIs. D-mannitol was selected as a model carrier. The materials were characterized concerning their different particle properties and their charge was analysed alone and in blends before and after flow over a stainless-steel pipe.

Results: The spray-dried SBS (amorphous and spherical) charged positively and to a higher extent than jet milled SBS (crystalline and acicular) that charged negatively and to a lower extent. D-mannitol charged positively and to a higher extent than the APIs. All drug-excipient blends charged negatively and differences were found between the spray-dried and jet milled SBS blends at 2% and 5% drug loads.

Conclusions: It was demonstrated how distinct solid-states, particle shape, size and morphology as well as different water contents of the different materials can affect tribo-charging. For their binary blends, the amount and nature of fines seem to govern inter-particle contacts critically impacting charge evolution.

Keywords: dry powder inhaler (DPI); inhalation; particle/material properties; powder blends; powder processing.

MeSH terms

  • Administration, Inhalation
  • Albuterol / administration & dosage*
  • Chemistry, Pharmaceutical / methods
  • Drug Carriers / chemistry
  • Dry Powder Inhalers
  • Excipients / chemistry
  • Humans
  • Mannitol / chemistry*
  • Particle Size
  • Powders / chemistry
  • Surface Properties

Substances

  • Drug Carriers
  • Excipients
  • Powders
  • Mannitol
  • Albuterol