Surface Energy Determined by Inverse Gas Chromatography as a Tool to Investigate Particulate Interactions in Dry Powder Inhalers

Dry powder inhalers (DPIs) usually contain drug particles <6 μm which agglomerate and/ or adhere on the surfaces of large carriers particles. The detachment of drug particles from carriers and de-agglomeration of drug particles into primary particles is essential for drug deposition in the deep lung. These processes are influenced by the surface energy of particles. Inverse gas chromatography (IGC) has been used to determine the surface energy of powder particles used in DPI to characterize materials and to understand aerosolization behaviour. Early studies used an infinite dilution technique to determine nonpolar surface energy and free energy of adsorption for polar interactions separately. Although some correlations were observed with the change in nonpolar surface energy before and after micronization, milling and storage, a lack of consistency in the change of free energy of adsorption was common. Moreover, a consistent relationship between complex de-agglomeration behaviour and surface energy has not been established and there are even some examples of negative correlation. In fact, nonpolar surface energy at infinite dilution is an incomplete representation of powder surface characteristics. The techniques for measuring polar surface energy, total surface energy and surface energy distribution have provided more revealing information about surface energetics of powders. Surface energy distributions determined by IGC or surface energy analyser have been successfully used to understand energetic heterogeneity of surfaces, characterize different polymorphs and understand changes due to micronization, structural relaxation, dry coating and storage. Efforts have been made to utilize surface energy distribution data to calculate powder strength distribution and to explain complex de-agglomeration behaviour of DPI formulations.