Adhesion and Dispersion of Salmeterol Xinafoate from Lactose Interactive Mixtures for Inhalation - Can Surface Roughness of Carriers Predict Performance?

  • Dr Nazrul Islam, Pharmacy Section, School of Life Sciences, Queensland University of Technology, Brisbane QLD-4001, Australia
  • Prof Peter Stewart, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Vic 3250, Australia
  • Dr Ian Larson, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Vic 3250, Australia
  • Dr Patrick Hartely, CSIRO Molecular & Health Technologies, Clayton, VIC 3169, Australia
  • Objective: The objective was to understand the influence of the surface roughness of lactose carriers on the adhesion and dispersion of salmeterol xinafoate (SX) from interactive mixtures. Methods: The surface roughness of lactose carriers was determined by confocal microscopy. Particle images and adhesion forces between SX and lactose particles were determined by Atomic Force Microscopy. The dispersion of SX (2.5%) from interactive mixtures with lactose was determined using a twin-stage impinger with a Rotahaler® at an airflow rate of 60L/min. SX was analysed using a validated HPLC assay. Results: The RMS Rq of lactose carriers ranged from 0.93-2.84μm, the Fine Particle Fraction (FPF) of SX ranged between 4 and 24 percent and average adhesion force between a SX and lactose particles ranged between 49 and 134 nN. Conclusions: No direct correlation was observed between the RMS Rq of lactose carriers and either the FPF of SX for the interactive mixtures or the adhesion force of a SX on the lactose particles; however, the presence of fine lactose associated with the carrier surface increased the FPF of SX. Dispersion through direct SX detachment from the carrier surface is not consistent with the poor correlations described and is more likely to occur through complex particulate interactions involving fine lactose.