Permeability as a performance descriptor of dry powder inhalation carriers: Investigation of several lactose grades

Authors: , ,

Background: Dry powder inhalers (DPIs) have captured the interest of several research groups, for the purpose of solving the performance prediction dilemma. Several studies reported linear inverse relationship between permeability and inhalation performance, while others found no simple relationships. The carrier particle sizes used in these studies were different, that may have resulted in viewing only a part of the whole pattern in each study.
Aim: This study aimed to investigate the relationship between the carrier permeability and the performance of the DPIs and to utilize this relationship in formulation development.
Methods: We prepared inhalation mixtures from six different lactose grades. Carriers and inhalation mixtures were characterized for their particle size distribution using laser diffraction, crystallinity using differential scanning calorimetry, particle shape using image analysis, moisture contents using loss on drying, pore size distribution and permeability using mercury porosimetry. We assessed the in vitro performance of the inhalation mixtures.
Results: The results show that carriers were crystalline with low moisture contents. However, carriers differed in their size distributions, permeabilities and performance (FPF8.06 5 – 21 %).
Conclusions: Initially at low permeabilities, the increase in performance was associated with increasing carrier permeability, until an optimum performance was reached. At higher permeabilities, a decrease in performance was associated with increasing carrier permeability. The findings explain reported controversies between carrier permeability and performance. Carriers with excessive amount of fines become highly resistant to air flow with lower dispersion/performance. Permeability can account for carrier size distribution, shape and packing in a more performance-relevant manner, it also allows identifying a carrier’s optimum fines content to meet device dispersion requirements.