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 excipients and physical characteristics of inhalation particles on their in vitro aerosolization performance, and thereby to maximize their respirable fraction. Dry powders were produced by spray-drying using excipients that are FDA-approved for inhalation as lactose, materials that are endogenous to the lungs as albumin and dipalmitoylphosphatidylcholine (DPPC); and/or protein stabilizers as trehalose or mannitol. Dry powders suitable for deep lung deposition, i.e. with an aerodynamic diameter of individual particles <3 microm, were prepared. They presented 0.04--0.25 g/cm(3) bulk tap densities, 3--5 microm geometric particle sizes, up to 90% emitted doses and 50% respirable fractions in the Andersen cascade impactor using a Spinhaler inhaler device. The incorporation of lactose, albumin and DPPC in the formulation all 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 appropriately selecting composition and physical characteristics of the particles.
Bosquillon
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C
Université catholique de Louvain, School of Pharmacy, Department of Pharmaceutical Technology, UCL 73.20 avenue, E. Mounier 73, 1200 Brussels, Belgium.
Lombry
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C
Préat
V
V
Vanbever
R
R
D000280:Administration, Inhalation; D000336:Aerosols; D002626:Chemistry, Pharmaceutical; D005079:Excipients; D010316:Particle Size; D011208:Powders
D000336:Aerosols; D005079:Excipients; D011208:Powders