AAPS PharmSciTech

, Volume 19, Issue 5, pp 2247–2254 | Cite as

Spray-Freeze Drying: a Suitable Method for Aerosol Delivery of Antibodies in the Presence of Trehalose and Cyclodextrins

  • Maryam Amini Pouya
  • Behnaz Daneshmand
  • Shabnam Aghababaie
  • Homa FaghihiEmail author
  • Alireza VatanaraEmail author
Research Article


We aimed to prepare spray-freeze-dried powder of IgG considering physicochemical stability and aerodynamic aspects. Spray-freeze drying (SFD) exposes proteins to various stresses which should be compensated by suitable stabilizers. The competence of cyclodextrins (CDs), namely beta-cyclodextrin (βCD) and hydroxypropyl βCD (HPβCD), at very low concentrations, was investigated in the presence of separate mannitol- and trehalose-based formulations. Spray-freeze-dried preparations were quantified in terms of monomer recovery and conformation by size exclusion chromatography (SEC-HPLC) and Fourier transform infrared (FTIR) spectroscopy, respectively. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) were employed to identify the thermal characteristics of powders. Particle morphology was visualized by scanning electron microscopy (SEM). Aerodynamic behavior of powders was checked through an Anderson cascade impactor (ACI). Although all formulations protected antibody from aggregation during the SFD process (aggregation < 1%), mannitol-containing ones failed upon the storage (19.54% in the worst case). Trehalose-HPβCD incomparably preserved the formulation with fine particle fraction (FPF) of 51.29%. Crystallization of mannitol resulted in IgG destabilization upon storage. Although employed concentration of CDs is too low (less than 50:1 molar ratio to protein), they successfully served as stabilizing agents in SFD with perfect improvement in aerosol functionality.

Graphical Abstract


IgG spray-freeze drying cyclodextrins trehalose stability aerodynamic property 



Immunoglobulin G


Spray-freeze drying






Hydroxypropyl beta-cyclodextrin


Size exclusion high-performance liquid chromatography


Fourier transform infrared


Differential scanning calorimetry


X-ray diffraction


Scanning electron microscopy


Anderson cascade impactor


Freeze drying


Spray drying




Glass transition temperature


Recombinant human deoxyribonuclease


Hydroxypropyl methylcellulose


Intravenous immunoglobulin




Fine particle fraction


Lactate dehydrogenase


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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutics, Faculty of PharmacyTehran University of Medical SciencesTehranIran

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