Production of inhalable drug particles traditionally involves milling, spray drying, spray freeze drying and supercritical fluid processes. Many of these processes expose the formulation to thermal or mechanical stresses, leading to changes in the particles’ surface and physicochemical properties. Among various particle properties (particle size and size distribution, surface properties, hygroscopicity, electrostatic charge and relative humidity), surface roughness, hydrophobicity and composition have pivotal impact on the interparticle interactions, aerosolization behavior, dissolution and stability of an inhalable product. Various advanced surface characterization techniques such as atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and time of flight secondary ion mass spectrometry (ToF-SIMS) have been used to determine the surface chemistry of dry powder formulations and the effects of the particle surface chemical properties on the dissolution and aerosol performance of dry powder inhalers (DPIs). This article discusses surface analytical techniques and applications in dry powder formulation characterization.
Applications of surface analytical techniques in characterization of dry powder formulations
Surface composition and interfacial properties of dry powder particles play a significant role in the processing, structure and functionality of orally inhaled dry powders. Therefore, advanced surface characterization techniques, such as AFM, XPS and ToF-SIMS, are critical to better understanding powder behavior in the early stages of DPI formulation, which may help avoid stability issues later in development.