It is a well-known formulation concept to increase the fine particle fraction (FPF) of dry powder inhalers (DPIs) by the addition of lactose fines. Usually during a first mixing step lactose carrier particles and fines are blended. In a second mixing step the API is added and ternary mixtures between the lactose carrier, the lactose fines and the API form. As all commercially available lactose fines are produced by milling little is known about the influence of the origin of the fines and hence the physico-chemical properties of the fines on the DPI performance. For this reason the aim of this work was to study the influence of intrinsic fines, which were prepared during the crystallization of the carrier material, and extrinsic milled fines, which were added to a carrier with a reduced fines content in a separate mixing step, on the performance of a DPI formulation. Adhesive mixtures with a hydrophilic (salbutamol sulfate) and a lipophilic (budesonide) API and three different carrier combinations (lactose RF “reduced fines”, lactose IF “intrinsic fines” and lactose EF “extrinsic fines”) were prepared and further analyzed.
Only the presence of externally added milled fines increased the FPF. The presence of intrinisic fines did not improve the FPF. The physico-chemical properties of the carrier combinations assessed in this study such as amorphous content and surface energy couldn´t be used to predict the performance of the formulation.