Mj. Clarke et al., Physicochemical factors governing the performance of nedocromil sodium as a dry powder aerosol, J PHARM SCI, 89(9), 2000, pp. 1160-1169
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.