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Stabilization of proteins in solid form.
Cicerone, Marcus T; Pikal, Michael J; Qian, Ken K.
Afiliação
  • Cicerone MT; Materials Measurement Lab, National Institute of Standards and Technology, Gaithersburg, MD 20899-8543, USA; Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA. Electronic address: cicerone@nist.gov.
  • Pikal MJ; Pharmaceutical Sciences Dept., University of Connecticut, Storrs, CT 06269, USA.
  • Qian KK; Materials Measurement Lab, National Institute of Standards and Technology, Gaithersburg, MD 20899-8543, USA.
Adv Drug Deliv Rev ; 93: 14-24, 2015 Oct 01.
Article em En | MEDLINE | ID: mdl-25982818
Immunogenicity of aggregated or otherwise degraded protein delivered from depots or other biopharmaceutical products is an increasing concern, and the ability to deliver stable, active protein is of central importance. We review characterization approaches for solid protein dosage forms with respect to metrics that are intended to be predictive of protein stability against aggregation and other degradation processes. Each of these approaches is ultimately motivated by hypothetical connections between protein stability and the material property being measured. We critically evaluate correlations between these properties and stability outcomes, and use these evaluations to revise the currently standing hypotheses. Based on this we provide simple physical principles that are necessary (and possibly sufficient) for generating solid delivery vehicles with stable protein loads. Essentially, proteins should be strongly coupled (typically through H-bonds) to the bulk regions of a phase-homogeneous matrix with suppressed ß relaxation. We also provide a framework for reliable characterization of solid protein forms with respect to stability.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas / Sistemas de Liberação de Medicamentos / Estabilidade de Medicamentos Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas / Sistemas de Liberação de Medicamentos / Estabilidade de Medicamentos Idioma: En Ano de publicação: 2015 Tipo de documento: Article