Influence of excipients and storage humidity on the deposition of disodium cromoglycate (DSCG) in the Twin Impinger

The in vitro deposition pattern of disodium cromoglycate (DSCG) from a unit dose dry powder inhaler device (Microhaler(R)) was investigated using the Twin Impinger. Four excipients with differing particle sizes, two alpha-lactose monohydrate grades (Pharmatose 325 M, x(50) = 56.3 mu m and Granulac 220, x(50) = 15.6 mu m) and two dextrose monohydrate grades (Roferose FF, x(50) = 102.8 mu m and Roferose SF, x(50) = 37.4 mu m), were mixed with DSCG in the ratio 1 plus 1 and 1 plus 4 at low relative humidity. Loose spherical agglomerates were formed in a rotating drum and then the mixtures were filled into hard gelatin capsules size 3 and stored at 33 and 55% RH, respectively. The deposition pattern was investigated using the Twin Impinger at a flow rate of 60 l/min. The amount of DSCG deposited in the lower impingement chamber, corresponding to a particle size of less than or equal to 6.4 mu m, was markedly influenced by the humidity level during storage. In all experiments, the fine particle fraction from mixtures stored at 33% RH was higher compared to those stored at 55% RH. Mixtures containing 1 part DSCG plus 1 part excipient showed higher deposition rates than the 4 + 1 mixtures. Excipients with a smaller mean particle diameter gave a higher DSCG deposition in the lower impingement chamber. Best results were obtained with the 1 + 1 mixtures of DSCG and fine lactose (Granulac 220) with 41% and DSCG and fine glucose (Roferose SF) with 38%, respectively. The results indicate that dry powder inhalations can be optimized by appropriate selection of the excipient, because its particle size distribution and its proportion in a formulation in combination with the storage humidity are important factors determining the inhalation fraction of a formulation.