title: Design and Evaluation of the Highly Concentrated Human IgG Formulation Using Cyclodextrin Polypseudorotaxane Hydrogels.
abstract: To achieve the potent therapeutic effects of human immunoglobulin G (IgG), highly concentrated formulations are required. However, the stabilization for highly concentrated human IgG is laborious work. In the present study, to investigate the potentials of polypseudorotaxane (PPRX) hydrogels consisting of polyethylene glycol (PEG) and α- or γ-cyclodextrin (α- or γ-CyD) as pharmaceutical materials for highly concentrated human IgG, we designed the PPRX hydrogels including human IgG and evaluated their pharmaceutical properties. The α- and γ-CyDs formed PPRX hydrogels with PEG (M.W. 20,000) even in the presence of highly concentrated human IgG (>100 mg/mL). According to the results of (1)H-NMR, powder X-ray diffraction, and Raman microscopy, the formation of human IgG/CyD PPRX hydrogels was based on physical cross-linking arising from their columnar structures. The release profiles of human IgG from the hydrogels were in accordance with the non-Fickian diffusion model. Importantly, the stabilities of human IgG included into the hydrogels against thermal and shaking stresses were markedly improved. These findings suggest that PEG/CyD PPRX hydrogels are useful to prepare the formulation for highly concentrated human IgG.
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Higashi
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Tajima
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ohshita
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.|Program for Leading Graduate Schools "HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, Kumamoto, Japan.
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Hirotsu
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.|Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
authors.forename: Irhan Ibrahim
authors.initials: II
authors.lastname: Abu Hashim
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.affiliation: R&D Headquarters, Terumo Corporation, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa, 259-0151, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Koyama
authors.affiliation: R&D Headquarters, Terumo Corporation, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa, 259-0151, Japan.
authors.forename: Ruriko
authors.initials: R
authors.lastname: Iibuchi
authors.affiliation: R&D Headquarters, Terumo Corporation, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa, 259-0151, Japan.
authors.forename: Shiuhei
authors.initials: S
authors.lastname: Mieda
authors.affiliation: R&D Headquarters, Terumo Corporation, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa, 259-0151, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Handa
authors.affiliation: R&D Headquarters, Terumo Corporation, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa, 259-0151, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kimoto
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan. arimah@gpo.kumamoto-u.ac.jp.|Program for Leading Graduate Schools "HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, Kumamoto, Japan. arimah@gpo.kumamoto-u.ac.jp.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003505:Cyclodextrins / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D043862:Rotaxanes / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods; D047408:gamma-Cyclodextrins / Q000737:chemistry
chemical_list: D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D007074:Immunoglobulin G; D043862:Rotaxanes; D047408:gamma-Cyclodextrins; D011092:Polyethylene Glycols; C023792:gamma-cyclodextrin
keywords: cyclodextrin; human IgG; hydrogel; polypseudorotaxane; stability