RETENTION OF THE AMORPHOUS STATE OF TREHALOSE AT HIGH RELATIVE HUMIDITY USING ORGANIC SALT ADDITIVES: A MECHANISTIC UNDERSTANDING
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University of North Carolina at Charlotte
The glassy or amorphous solid state of trehalose has been utilized in the food and pharmaceutical industry to immobilize and stabilize sensitive molecules and it is increasingly being explored for the preservation of biologics. Retention of the glassy state is very dependent on the local humidity, as water is a known plasticizer that will decrease the glass transition temperature (Tg) of the solution, resulting in increased molecular mobility. If the storage temperature exceeds the Tg, the sample will generally crystallize at a rate that is dependent on the temperature and composition of the mixture. In order to preserve biologics during storage for extended times, delaying crystallization and retaining the amorphous state under adverse moisture excursions is desirable. Additives, such as polymers, other sugars, and salts have been used to modify the physical properties to increase the stability of trehalose glasses. Salts are of special interest due to the presence of pH buffering electrolytes in many formulations designed for biological systems. In this work the Tg of trehalose and salt compositions were determined using a dynamic mechanical analyzer (DMA) and the crystallization kinetics and sorption isotherms were studied by dynamic vapor sorption (DVS) method. Sorption isotherms were fitted to the Brunauer–Emmett–Teller (BET) equation to gain insight into the microstructure and localized interactions in order to develop an improved understanding of metastability above Tg. With this knowledge, we were able to identify and confirm a superior class of organic salt additives for stabilizing the amorphous state of trehalose.
Keanini, RussellJacobs, DonaldKrueger, Joanna
Thesis (Ph.D.)--University of North Carolina at Charlotte, 2018.
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