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

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.

Lyophilization of Liposomal Formulations: Still Necessary, Still Challenging

“…In another words, the maximally freeze concentrated solution becomes glass below T g ’ reaching viscosity values to the order of 10 13–14 P; whereas increasing the temperature above T g ’ results in an increase in mobility and the system changes to rubbery or liquid phase. This transition can occur over a broad temperature range [ 43 ].…”

The effect of mAb and excipient cryoconcentration on long-term frozen storage stability – Part 1: Higher molecular weight species and subvisible particle formation

“…In such cases, the onset of T g ′ can be determined using the first derivative plot. However, this inevitably leads to a deviation between the obtained T g ′ and the commonly reported midpoint T g ′ ( Pansare and Patel, 2016 ). Therefore, we optimised the sample preparation in order to directly measure the midpoint T g ′, based on the inflection point, of samples that only consist of a mAb and the buffer component.…”

“…The focus was on minimum and maximum mAb and histidine concentrations. DSC thermograms of protein samples that do not contain glass formers such as sugars often do not show a sharp sigmoidal change in heat flow signal ( Pansare and Patel, 2016 ). In such cases, the onset of T g ′ can be determined using the first derivative plot.…”

Effect of Freeze-Drying on Quality and Grinding Process of Food Produce: A Review

“…This phenomenon occurs when the solid matrix of the foodstuff can no longer support its weight, leading to drastic structural changes shown as a marked decrease in volume, increase in the stickiness of dry powders, and loss of porosity. The collapse temperature is related to the T g of the maximally frozen concentrated solute [51], and it represents the temperature above which the solute matrix loses its shape and quality is decreased. Therefore the relationship between rehydration and T g should be interpreted from porosity and collapse during freeze-drying.…”