Investigation of the physical properties of spray-dried stabilised lysozyme particles

Abstract

The aim of this study was to investigate the effect of the composition of formulations on the physical properties, including glass-transition temperatures (Tg) and aerodynamic-related characteristics, of spray-dried lysozyme particles. The Tg, as determined by differential scanning calorimetry, of spray-dried lysozyme formulations was found to be dependent upon the type and amount of excipient(s) included in the formulation. In addition, the Tg of sucrose-containing particles appeared to be raised markedly by the inclusion of trehalose, but not by dextran. The surfaces of all spray-dried particles were shown by scanning electron microscopy to be smooth with some containing characteristic dimples, typical of spray-dried material, and the morphology appeared to be independent of variation in excipient composition. However, the volume median diameters (VMD) of spray-dried powders, as determined by laser diffraction, were found to depend upon the amounts of excipients. The fine particle fraction of enzyme delivered to the lower stage of a twin-stage impinger from lysozyme–trehalose 1:1 powders appeared to be greater than that from lysozyme–sucrose 1:1 particles (22.5% vs 15.9%) when dispersed via a Rotahaler although a similar dispersibility of the two formulations (39.6% vs 36.7%) was found from a glass inhaler. In general, spray-drying was demonstrated to be feasible to produce respirable particles of the stabilised model protein, with Tg of the formulations being >30°C higher than room temperature.