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Recently, the portfolio of compounds approved for inhalation therapy has expanded rapidly for lung disease therapies. The rationale for this delivery approach includes a more targeted and localized delivery to the diseased site with reduced systemic exposure, potentially leading to decreased adverse side effects. We have proposed that brittle matrix powders prepared by thin film freezing (TFF) are a suitable platform for pulmonary drug delivery which can achieve high lung concentrations while limit the corresponding systemic levels associated with toxicity, and enhanced physicochemical and aerodynamic properties can be obtained by varying TFF processing parameters. In Chapter 2, the in vitro and in vivo performance of an amorphous formulation prepared by TFF and a crystalline micronized formulation produced by milling was compared for Tacrolimus (TAC). TFF processed matrix powders was capable of achieving deep lung delivery due to its low density, highly porous and brittle characteristics. When emitted from a Miat® monodose inhaler, TFF processed TAC formulations exhibited a fine particle fraction (FPF) of 83.3% and a mass median aerodynamic diameter (MMAD) of 2.26 µm. Single dose 24-h pharmacokinetic studies in rats demonstrated that the TAC formulation prepared by TFF exhibited higher pulmonary bioavailability with a prolonged retention time in the lung, possibly due to decreased clearance (e.g., macrophage phagocytosis), compared to the micronized TAC formulation. Additionally, TFF formulation generated a lower systemic TAC concentration with smaller variability than the micronized formulation following inhalation, potentially leading to reduced side effects related to the drug in systemic circulation. Chapter 3 investigated the impact of processing parameters in the TFF process on the physicochemical and aerodynamic properties of the resulting formulations. All of these enhanced powder properties resulted from higher freezing rate contributed to a better aerodynamic performance of the obtaining formulations. Moreover, a decreasing trend of FPF was observed for these TFF powders when the initial solid concentrations increased. The variation of the freezing rate and initial solid loading in the TFF process enabled the production of formulations with enhanced physicochemical properties and improved aerodynamic performance.