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Practical Considerations for Determination of Glass Transition Temperature of a Maximally Freeze Concentrated Solution

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ABSTRACT

Glass transition temperature is a unique thermal characteristic of amorphous systems and is associated with changes in physical properties such as heat capacity, viscosity, electrical resistance, and molecular mobility. Glass transition temperature for amorphous solids is referred as (T g), whereas for maximally freeze concentrated solution, the notation is (T g′). This article is focused on the factors affecting determination of T g′ for application to lyophilization process design and frozen storage stability. Also, this review provides a perspective on use of various types of solutes in protein formulation and their effect on T g′. Although various analytical techniques are used for determination of T g′ based on the changes in physical properties associated with glass transition, the differential scanning calorimetry (DSC) is the most commonly used technique. In this article, an overview of DSC technique is provided along with brief discussion on the alternate analytical techniques for T g′ determination. Additionally, challenges associated with T g′ determination, using DSC for protein formulations, are discussed. The purpose of this review is to provide a practical industry perspective on determination of T g′ for protein formulations as it relates to design and development of lyophilization process and/or for frozen storage; however, a comprehensive review of glass transition temperature (T g, T g′), in general, is outside the scope of this work.

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Notes

  1. Detailed review on degree of supercooling and freezing mechanism is described in (5–7) and is not the focus of this work.

  2. Exact moisture level at the end of primary drying may vary based on the formulation components and the freeze drying cycle (16,17).

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  1. Department of Formulation Sciences, MedImmune, One MedImmune Way, Gaithersburg, Maryland, 20878, USA

    Swapnil K. Pansare & Sajal Manubhai Patel

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Pansare, S.K., Patel, S.M. Practical Considerations for Determination of Glass Transition Temperature of a Maximally Freeze Concentrated Solution. AAPS PharmSciTech 17, 805–819 (2016). https://doi.org/10.1208/s12249-016-0551-x

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