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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
First Online:

Abstract

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

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KEY WORDS

IgG spray-freeze drying cyclodextrins trehalose stability aerodynamic property 

Abbreviations

IgG

Immunoglobulin G

SFD

Spray-freeze drying

CDs

Cyclodextrines

βCD

Beta-cyclodextrin

HPβCD

Hydroxypropyl beta-cyclodextrin

SEC-HPLC

Size exclusion high-performance liquid chromatography

FTIR

Fourier transform infrared

DSC

Differential scanning calorimetry

XRD

X-ray diffraction

SEM

Scanning electron microscopy

ACI

Anderson cascade impactor

FD

Freeze drying

SD

Spray drying

w/v

Weight/volume

Tg

Glass transition temperature

rhDNAse

Recombinant human deoxyribonuclease

HPMC

Hydroxypropyl methylcellulose

IVIG

Intravenous immunoglobulin

i.t.

Intratracheally

FPF

Fine particle fraction

LDH

Lactate dehydrogenase

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© 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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