Prediction of Dry Powder Inhaler Formulation Performance From Surface Energetics and Blending Dynamics

Abstract

The purpose of these studies was to investigate the ability of surface energy measurements and rates of mixing in dry powder inhaler (DPI) formulations to predict aerosol dispersion performance. Two lactose carrier systems comprising either spray-dried or milled particles were developed such that they had identical physical characteristics except for surface morphology and surface energies avoiding confounding variables common in other studies. Surface energy measurements confirmed significant differences between the powder systems. Spray-dried lactose had a higher surface entropy (0.20 vs. 0.13 mJ/m²K) and surface enthalpy (103.2 vs. 79.2 mJ/m²) compared with milled lactose. Mixing rates of budesonide or fluorescein were assessed dynamically, and significant differences in blending were observed between lactose systems for both drugs. Surface energies of the lactose carriers were inversely proportional to dispersion performance. In addition, the root mean square (RMS) of blending rates correlated positively with aerosol dispersion performance. Both techniques have potential utility in routine screening of DPI formulations.

Keywords:

• inverse gas chromatography
• mixing
• lactose
• aerosol

ACKNOWLEDGMENTS

Authors acknowledge the generosity of Lactose New Zealand (DMV-Fonterra Excipients) for providing lactose samples used in these studies. Martin Telko gratefully acknowledges past support from a U.S. Pharmacopeia Graduate Fellowship and current support from a PhRMA Foundation Pre-Doctoral Fellowship.