title: Application of cyclodextrins in antibody microparticles: potentials for antibody protection in spray drying.
abstract: OBJECTIVE
  Dry powder formulations are extensively used to improve the stability of antibodies. Spray drying is one of important methods for protein drying. This study investigated the effects of trehalose, hydroxypropyl beta cyclodextrin (HPBCD) and beta cyclodextrin (BCD) on the stability and particle properties of spray-dried IgG.
  
  
  METHODS
  D-optimal design was employed for both experimental design and analysis and optimization of the variables. The size and aerodynamic behavior of particles were determined using laser light scattering and glass twin impinger, respectively. In addition, stability, ratio of beta sheets and morphology of antibody were analyzed using size exclusion chromatography, IR spectroscopy and electron microscopy, respectively.
  
  
  RESULTS
  Particle properties and antibody stability were significantly improved in the presence of HPBCD. In addition, particle aerodynamic behavior, in terms of fine-particle fraction (FPF), enhanced up to 52.23%. Furthermore, antibody was better preserved not only during spray drying, but also during long-term storage. In contrast, application of BCD resulted in the formation of larger particles. Although trehalose caused inappropriate aerodynamic property, it efficiently decreased antibody aggregation.
  
  
  CONCLUSIONS
  HPBCD is an efficient excipient for the development of inhalable protein formulations. In this regard, optimal particle property and antibody stability was obtained with proper combination of cyclodextrins and simple sugars, such as trehalose.
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , Shahid Sadoughi University of Medical Sciences , Yazd , Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Ramezani
authors.affiliation: b Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Vatanara
authors.affiliation: c Department of Pharmacology, School of Medicine , Bushehr University of Medical Sciences , Bushehr , Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Seyedabadi
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , Shahid Sadoughi University of Medical Sciences , Yazd , Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Nabi Meibodi
authors.affiliation: d Department of Physiology, School of Medicine , Zahedan University of Medical Sciences , Zahedan , Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Fanaei
mesh_terms: D000280:Administration, Inhalation; D000906:Antibodies / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry*; D003890:Desiccation; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D010316:Particle Size; D011208:Powders / Q000737:chemistry*; D014199:Trehalose / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000906:Antibodies; D003505:Cyclodextrins; D005079:Excipients; D011208:Powders; D047392:beta-Cyclodextrins; D014199:Trehalose; C031215:betadex
keywords: Antibody; D-optimal; beta cyclodextrin; hydroxypropyl beta cyclodextrin; spray dry; trehalose