Influence of formulation excipients and physical characteristics of inhalation dry powders on their aerosolization performance

The objective of this study was to determine the effects of formulation exc ipients and physical characteristics of inhalation particles on their in vi tro aerosolization performance, and thereby to maximize their respirable fr action. Dry powders were produced by spray-drying using excipients that are FDA-approved for inhalation as lactose, materials that are endogenous to t he lungs as albumin and dipalmitoylphosphatidylcholine (DPPC); and/or prote in stabilizers as trehalose or mannitol. Dry powders suitable for Jeep lung deposition, i.e. with an aerodynamic diameter of individual particles <3 < mu>m, were prepared. They presented 0.04-0.25 g/cm(3) bulk tap densities, 3 -5 mum geometric particle sizes, up to 90% emitted doses and 50% respirable fractions in the Andersen cascade impactor using a Spinhaler(TM) inhaler d evice. The incorporation of lactose, albumin and DPPC in the formulation al l improved the aerosolization properties, in contrast to trehalose and the mannitol which decreased powder flowability. The relative proportion of the excipients affected aerosol performance as well. The lower the bulk powder tap density, the higher the respirable fraction. Optimization of in vitro aerosolization properties of inhalation dry powders can be achieved by appr opriately selecting composition and physical characteristics of the particl es. (C) 2001 Elsevier Science B.V. All rights reserved.