Physicochemical factors governing the performance of nedocromil sodium as a dry powder aerosol

Previous investigations have found that the in vitro aerosol performance of nedocromil sodium is poor. A study has been undertaken to gain a better un derstanding of the physicochemical properties of the drug particles togethe r with the factors governing the aerosol performance of inhalation systems containing this drug. Material previously passed through a hammer mill only and particles subsequently passed through a micronizer were characterized, and the information gathered was correlated with the in vitro aerosol perf ormance of the pure drug systems. Optimization of particle sizing procedure s revealed that both sets of materials were ultrafine powders with a :volum e median diameter of similar to 1 mu m. It is concluded that the processing stages, employed in the manufacture of these batches of fine particle nedo cromil sodium trihydrate, may not in fact be primary particle size reductio n stages but instead deaggregation stages and that these govern the aerosol performance. The in vitro aerosol performance of samples of the "micronize d" nedocromil sodium stored over a range of relative humidities (RHs) was c haracterized. Storage RHs in the range 12-76% (where nedocromil sodium is s table as the trihydrate) did not have a dramatic effect on the in vitro aer osol performance of the drug. However, conversion to the heptahemihydrate ( following storage of the drug at 86% RH) significantly decreased the deaggr egation performance in an in vitro model. (C) 2000 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 1160-1169, 2000.