Powder dispersion
One of the main criteria for the effective drug delivery via lungs is the size of the inhaled particle. Respirable size i.e. the particle is transported to deep lungs (alveoli region) is around 1 – 5 micrometers. The particle size can be easily controlled in the powder production. The powders, however, tend to stick to each other in the collection. Therefore, the dispersion and deagglomeration behavior of the powder should be studied.
The dispersion testing of the fine powders was conducted with the novel deagglomeration apparatus [14]. Powder agglomerates, i.e. the mixture of carrier and fine powders, is fed continuously through a narrow tube with the aid of thin air flow of 1.2 l/min. At the outlet of the needle the agglomerates are subjected to the main flow rate (QM) from 15 to 90 l/min intending to disperse the powder i.e. deagglomeration zone, see Figure 8. These QM values correspond to the jet Reynolds numbers from 8000 to 48000. The flow forms a highly turbulent space, i.e. the deagglomeration zone, where possible break-up of powder agglomerates takes place. The fine powder particles are isokinetically sampled from homogeneously mixed aerosol into low-pressure impactors. Fine particle fractions (FPF), mass medium aerodynamic diameter (MMAD), and size distribution can be determined at different flow rates.
Figure 9 illustrates a common trend in the change of the particle distribution at different flow rates. As seen, all the dispersed particles, in this case salbutamol 92 w% and L-leucine 8 w%, are within the respirable size range. Also, the increase in the flow rate from 15 to 90 l/min improved the powders dispersion (the increase in particle concentration) and deagglomeration (the size of the dispersed particles decreases).
In dry powder inhaler the fine drug particles are commonly mixed with large lactose particles. These lactose carriers aid the dispersion of fine particles. Figure 10 shows the fine particle fractions of the peptide-coated drug powders that were introduced to the dispersion testing without lactose carriers. The powders with crystalline L-leucine surface exhibited good flowability that made possible to feed these powders as such i.e. without carrier particles. More importantly, they showed excellent deagglomeration performance even at very low flow rate.
