Immobilization of fine particles on lactose carrier by precision coating and its effect on the performance of dry powder formulations

The feasibility of immobilization of fine particles on a lactose carrier by precision coating and producing carrier particles of different surface roughness from the same core was explored. A relationship between the resultant surface roughness of the carrier and the in vitro deposition pattern of salbutamol sulfate was established. Lactose carrier particles in the precision coating chamber were spray coated with liquid suspensions consisting of micronized lactose dispersed in isopropyl alcohol (IPA) and/or water mixtures. The surface-modified lactose particles were fractionated and then characterized by laser diffraction for size, image analysis for shape, and scanning probe microscopy for surface roughness. The in vitro deposition pattern of salbutamol sulfate from the drug-lactose mixtures was determined with the twin-stage glass impinger and expressed as the fine particle fraction and dispersibility of the drug. Immobilization of fine particles on carrier particles was feasible by the precision coating process as shown by the scanning probe topographs and the roughness values of the carrier particles. Generally, more discrete fine particles were deposited on the carrier surface and a higher surface roughness was seen when the spray suspension consisting of a higher proportion of IPA was used. A significant correlation was found between the fine particle fraction of salbutamol sulfate with the roughness of lactose. This relationship established between the in vitro drug deposition pattern and the microscopic surface roughness of the carrier would be helpful in the optimization of drug delivery to targeted areas in the lungs. (C) 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association.