PMID: 9165529May 1, 1997Paper

The relationship between protein aggregation and molecular mobility below the glass transition temperature of lyophilized formulations containing a monoclonal antibody

Pharmaceutical Research
S P DudduP R Dal Monte

Abstract

To find out if the physical instability of a lyophilized dosage form is related to molecular mobility below the glass transition temperature. Further, to explore if the stability data generated at temperatures below the glass transition temperature can be used to predict the stability of a lyophilized solid under recommended storage conditions. The temperature dependence of relaxation time constant, tau, was obtained for sucrose and trehalose formulations of the monoclonal antibody (5 mg protein/vial) from enthalpy relaxation studies using differential scanning calorimetry. The non-exponentiality parameter, beta, in the relaxation behavior was also obtained using dielectric relaxation spectroscopy. For both sucrose and trehalose formulations, the variation in tau with temperature could be fitted Vogel-Tammann-Fulcher (VTF) equation. The two formulations exhibited difference sensitivities to temperature. Sucrose formulation was more fragile and exhibited a stronger non-Arrhenius behavior compared to trehalose formulation below glass transition. Both formulations exhibited < 2% aggregation at t/tau values < 10, where t is the time of storage. Since the relaxation times for sucrose and trehalose formulations at 5 degrees C are on ...Continue Reading

Citations

Feb 10, 2010·Pharmaceutical Research·Mark Cornell ManningDerrick S Katayama
Nov 7, 2019·Pharmaceutical Development and Technology·Faten MadaniPierre Tchoreloff
Jun 7, 2008·Journal of Biomaterials Science. Polymer Edition·Peng WuDavid W Grainger
Jun 2, 2005·Pharmaceutical Development and Technology·J Jeff SchwegmanMichael J Akers
May 3, 2005·Chemical & Pharmaceutical Bulletin·Kazuyuki TanakaTeruyuki Kitagawa
Jan 3, 2006·Diabetes Technology & Therapeutics·Steven WhiteNancy J Harper
Aug 31, 2006·Pharmaceutical Research·Sheri L ShamblinMichael J Pikal
Jan 5, 2017·Drug Development and Industrial Pharmacy·Yanan CuiHua Guan
Feb 1, 2017·Computational and Structural Biotechnology Journal·Maria Monica CastellanosJoseph E Curtis
May 13, 2009·Molecular Pharmaceutics·Deliang ZhouEric A Schmitt
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Jun 23, 2004·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Yong-Hong LiaoGary P Martin
Dec 10, 1999·Journal of Pharmaceutical Sciences·J M SarciauxS L Nail
Jun 28, 2019·Molecular Pharmaceutics·Rajashekar Kammari, Elizabeth M Topp
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Jul 2, 2009·Journal of Pharmaceutical Sciences·Liuquan Lucy Chang, Michael J Pikal
Feb 22, 2011·Journal of Pharmaceutical Sciences·Satoshi Ohtake, Y John Wang

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