The formulation of powder inhalation systems containing a high mass of nedocromil sodium trihydrate

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.