Mj. Clarke et al., The formulation of powder inhalation systems containing a high mass of nedocromil sodium trihydrate, J PHARM SCI, 90(2), 2001, pp. 213-223
Nedocromil sodium trihydrate is not amenable to conventional methods of dry
powder inhaler formulation, including the preparation of coarse carrier sy
stems and aggregation of the pure drug powder. It is considered that the in
vitro aerosol performance of such systems is governed by the cohesive drug
-drug interactions. Therefore, alternative powder formulation strategies (n
ovel to nedocromil sodium) were developed. By decreasing the particle size
of the lactose carrier, the deaggregation and subsequent fine particle drug
deposition were significantly improved. Further improvements were made by
selecting and then optimizing high-shear mixing procedures. It was conclude
d, based on these findings and supportive microscopic studies (low-temperat
ure and environmental scanning electron microscopy together with energy-dis
persive X-ray analysis), that the FPL are producing their functional effect
s by intercalating within the drug self-agglomerates and physically disrupt
ing the cohesive drug-drug interactions. The use of a smaller-sized lactose
fraction in conjunction with a blending procedure capable of optimally dis
rupting the drug self-agglomerates allowed maximal intercalation of the exc
ipient material within the drug self-agglomerates. The adhesive drug-FPL in
teractions are considered to be weak compared with the cohesive drug-drug p
article interactions, cohesive interactions that would normally govern the
aerosol performance of powder systems containing a high mass of nedocromil
sodium trihydrate. (C) 2001 Wiley-Liss, Inc.