A novel spray-drying technique to produce low density particles for pulmonary delivery

Abstract

To date, all marketed DPI products rely on jet-milled, micronized drugs. Micronization often leads to drug powders exhibiting a large hydrophobic surface area resulting in strong cohesive forces, agglomeration and unsuitable aerosolization properties. In the current study, a new approach to prepare low density drug particles is described. Briefly, an oil-in-water emulsion consisting of an aqueous phase containing the dissolved model drug salbutamol sulphate, suitable surfactants, such as poloxamer or phosphatidylcholine, and optionally a bulking agent like lactose or a cyclodextrin derivative, and a lipid-phase that essentially consists of a liquefied propellant is spray-dried. By means of this process particles of very low density (0.02 g/cm 3) and a drug load of 40% were prepared. The particle exhibit a porous to hollow structure, are thin-walled and of irregular shape. Depending on the composition of the aqueous phase, mean geometric particle sizes of <5 μm were obtained. It could be shown that a higher amount of poloxamer in the feed emulsion resulted in particles with improved dispersibility. Reducing the vapour pressure of the inner propellant phase by addition of dichloromethane decreased the agglomeration tendency of the powders as a result of the irregular particle morphology and, hence, resulted in higher fine particle fractions.