The Study of Phase Separation in Amorphous Freeze-Dried Systems. Part I: Raman Mapping and Computational Analysis of XRPD Data in Model Polymer Systems

Impact of Heat Treatment on the Physical Properties of Noncrystalline Multisolute Systems Concentrated in Frozen Aqueous Solutions

“…The solute miscibility information revealed by the thermal analysis has some limitations because at least a certain fraction of the components should be phase separated to show the transition detectable by DSC. 21 The reason the total solute concentration affected the occurrence of the phase separation remains unclear.…”

Heterogeneity of Protein Environments in Frozen Solutions and in the Dried State

“…A potential protein/polymer phase separation in human brain-derived neurotropic factor (BDNF) and BDNF-polyethylene glycol (PEG) co-lyophilized with dextran was suggested based on scanning electron microscopy [26]. Additional evidences of phase separation between proteins and polymers were obtained using Raman mapping, which detected amorphous/amorphous phase separation between a protein and a lyoprotector, e.g., in lactoglobulin-dextran system [27][28][29]. It was also shown that trehalose had a greater propensity for phase separation from protein than sucrose, with phase separation detected for lysozyme-trehalose and lactoglobulin-trehalose (but not for protein-sucrose) systems.…”

The Study of Amorphous Phase Separation in a Model Polymer Phase-Separating System Using Raman Microscopy and a Low-Temperature Stage: Effect of Cooling Rate and Nucleation Temperature

“…The analysis of freeze-dried samples was described in a previous work, [28] so only an overview of the data collection is presented here. Raman mapping was performed with a Renishaw Raman InVia microscope equipped with confocal capability, a 785 nm diode laser (50 mW) and a 1200 l/mm grating.…”

“…[22][23][24] The technique has seen routine use in recent decades in the pharmaceutical industry for investigation of composition heterogeneity in tablets and polymorph screening of excipients. [25][26][27] However, except for a recent feasibility study from this laboratory, [28] the Raman technique has not been exploited in the characterization of amorphous phase behavior in freeze-dried systems. Additionally, to our knowledge, there are no studies investigating the use of this technique for the investigation of amorphous phase separation during the freezing process.…”

“…Additionally, to our knowledge, there are no studies investigating the use of this technique for the investigation of amorphous phase separation during the freezing process. Previous work from our laboratory [28] focused on the application of a novel Raman mapping technique in the detection of amorphous phase separation in model polyvinylpyrrolidone (PVP)/dextran freeze-dried systems. The results of the study demonstrated the ability of Raman mapping to identify phase separation, and the Raman method is comparable to the use of DSC, which is used to identify multiple glass transitions in phase separated samples.…”