Abstract
The ice crystallization and melting in systems where the equilibrium state is difficult to reach is one of the growing areas in pharmaceutical freeze-drying research. The quality of the final freeze-dried product depends on the parameters of the cooling step, which affect the ice nucleation and growth. In this paper, we present a DSC study of ice crystallization and melting in a sucrose-water system. Using two different types of thermal cycles, we examine the influence of cooling and heating rates on the thermal behavior of sucrose-water solutions with water contents between 50 and 100 wt%.The DSC results show that low cooling rates provide crystallization at higher temperatures and lead to lower amount of non-freezing water. Consequently, the glass transition and ice melting properties observed upon heating depend on the cooling conditions in the preceding step. Based on the experimental results, we investigate the reasons for the existence of the two steps on DSC heating curves in sucrose-water systems: the glass transition step and the onset of ice melting. We show that diffusion of water can be the limiting factor for ice growth and melting in the sucrose-water system when the amorphous phase is in a liquid state. In particular, when the diffusion coefficient drops below 10−14 m2/sec, the ice crystals growth or melting becomes strongly suppressed even above the glass transition temperature. Understanding the diffusion limitations in the sucrose-water system can be used for the optimization of the freeze-drying protocols for proteins and probiotics.
Highlights
Freeze-drying of proteins and live cells from aqueous solutions with sugars is widely utilized in the pharmaceutical and food industry for preservation and long-term storage
Using Constant heating rate (CHR) experiments we highlight the influence of cooling rate on the amount of ice, while Equal rates (ER) experiments were used since they give the most accurate and reproducible results in characterization of glass transition.[16,17]
Based on DSC data, we present a study of influence of cooling and heating rates on thermal behavior in the sucrose-water system and the role of water diffusion in ice crystallization and melting
Summary
Freeze-drying of proteins and live cells from aqueous solutions with sugars is widely utilized in the pharmaceutical and food industry for preservation and long-term storage. Most of water molecules crystallizes into ice, a smaller part interacts with solutes (sugars, proteins, etc), stays unfrozen, and becomes glassy. The glassy state is a non-equilibrium state of matter, it is solid but disordered as a liquid. In systems prone to form a glass, it is very difficult to reach equilibrium,[1] and the actual state of the system is dependent on the sample history. Slow diffusion[2] and polymorphism[3] are examples of phenomena that hinder achieving the equilibrium state and present substantial challenges for experimental studies of pharmaceutical formulations. In a freeze-drying process, after freezing, the formulation contains ice crystals embedded in a nonequilibrium glassy matrix formed by sugars and other solutes
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