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Spray-Dried Inhalable Powder Formulations of Therapeutic Proteins and Peptides

Abstract

Respiratory diseases are among the leading causes of morbidity and mortality worldwide. Innovations in biochemical engineering and understanding of the pathophysiology of respiratory diseases resulted in the development of many therapeutic proteins and peptide drugs with high specificity and potency. Currently, protein and peptide drugs are mostly administered by injections due to their large molecular size, poor oral absorption, and labile physicochemical properties. However, parenteral administration has several limitations such as frequent dosing due to the short half-life of protein and peptide in blood, pain on administration, sterility requirement, and poor patient compliance. Among various noninvasive routes of administrations, the pulmonary route has received a great deal of attention and is a better alternative to deliver protein and peptide drugs for treating respiratory diseases and systemic diseases. Among the various aerosol dosage forms, dry powder inhaler (DPI) systems appear to be promising for inhalation delivery of proteins and peptides due to their improved stability in solid state. This review focuses on the development of DPI formulations of protein and peptide drugs using advanced spray drying. An overview of the challenges in maintaining protein stability during the drying process and stabilizing excipients used in spray drying of proteins and peptide drugs is discussed. Finally, a summary of spray-dried DPI formulations of protein and peptide drugs, their characterization, various DPI devices used to deliver protein and peptide drugs, and current clinical status are discussed.

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Funding

This work was supported by NIH R01HL137282 (HMM), P01HL103453 (HMM), R21AI135935 (HMM), R21AG054766 (HMM), and NIDA 5UG3DA047717 (HMM and RP).

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Conceptualization: Basanth Babu Eedara and Heidi M. Mansour; writing original draft preparation and editing: Basanth Babu Eedara, David Encinas, Wafaa Alabsi, Robin Polt, and Heidi M. Mansour; supervision: Heidi M. Mansour.

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Correspondence to Heidi M. Mansour.

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Eedara, B.B., Alabsi, W., Encinas-Basurto, D. et al. Spray-Dried Inhalable Powder Formulations of Therapeutic Proteins and Peptides. AAPS PharmSciTech 22, 185 (2021). https://doi.org/10.1208/s12249-021-02043-5

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KEY WORDS

  • biologics
  • inhalation
  • dry powder inhalers
  • particle engineering design
  • respiratory