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In Vitro and In Vivo Performance of Dry Powder Inhalation Formulations: Comparison of Particles Prepared by Thin Film Freezing and Micronization

  • Research Article
  • Theme: Advances in Formulation and Device Technologies for Pulmonary Drug Delivery
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Abstract

Recently, inhaled immunosuppressive agents have attracted increasing attention for maintenance therapy following lung transplantation. 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. In this study, the in vitro and in vivo performance of an amorphous formulation prepared by thin film freezing (TFF) and a crystalline micronized formulation produced by milling was compared for tacrolimus (TAC). Despite the relatively large geometric size, the TFF-processed formulation 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.

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Authors and Affiliations

  1. College of Pharmacy, The University of Texas at Austin, 2409 University Ave. Mail Stop 1920A, Austin, Texas, 78712, USA

    Yi-Bo Wang, Alan B. Watts, Sha Liu, Ayesha Batra & Robert O. Williams III

  2. Division of Pulmonary Diseases/Critical Care Medicine, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

    Jay I. Peters

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  1. Yi-Bo Wang
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Correspondence to Robert O. Williams III.

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Guest Editors: Paul B. Myrdal and Steve W. Stein

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Wang, YB., Watts, A.B., Peters, J.I. et al. In Vitro and In Vivo Performance of Dry Powder Inhalation Formulations: Comparison of Particles Prepared by Thin Film Freezing and Micronization. AAPS PharmSciTech 15, 981–993 (2014). https://doi.org/10.1208/s12249-014-0126-7

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