Physicochemical characterisation of inhalation grade lactose after the removal of intrinsic fines

Abstract

Lactose is a common excipient in Dry Powder Inhaler (DPI) formulations, used as a carrier for the micronized drug particles. The presence of intrinsic lactose fines in the formulation influences its performance and their role and interactions between the lactose carrier and the micronized drug is still not fully understood. As a first step towards this investigation, “clean” lactose, with removed fines, was produced via wet decantation. Ethanol and isopropyl alcohol have been used in wet decantation, successfully removing lactose fines from the surface of the coarse particles. Differential Scanning Calorimetry (DSC) was employed to show that the powders maintained their crystalline character. Scanning Electron Microscopy (SEM) showed tomahawk-shaped particles in all the powders and some surface alteration occurring after decantation. An airflow titration method using laser diffraction (LDA) allowed the estimation of the removal of fines as well as the particle size distributions, while the non-polar and the polar components of the surface energy of the powders were calculated via Inverse Gas Chromatography-Surface Energy Analysis (iGC-SEA). As both solvents successfully removed fines, we propose the addition of isopropyl alcohol in the list of organic solvents suitable for this purpose.