(T1130-12-72) Structures of Glasses Created by Multiple Kinetic Arrests

Purpose: Amorphous formulation has been widely used to deliver poorly soluble drugs. The glassy structure is expected to determine the performance of amorphous drugs. Our goal is to characterize the structure of glasses, determine how different structural features are frozen at the glass transition and provide the insight into the relationship between the structure and dynamics.

Methods: Itraconazole (ITZ) glasses of different structures were prepared by cooling at different rates. Structure of glasses and supercool liquids ware measured by synchrotron and conventional X-ray scattering. Fictive temperature of enthalpy was measured by Differential Scanning Calorimetry (DSC).

Results: We find that ITZ glasses prepared by cooling at different rates have very different structures with respect to smectic and lateral packing. By comparison with the equilibrium liquid, we find that each glass has structural characters that correspond to the freezing of the precursor liquid at very different temperatures; that is, the glass has different fictive temperatures with respect to different structural attributes. The regularity of smectic and lateral packing is frozen at a higher temperature than the molecular spacing between or within the layers. The former corresponds to the kinetic arrest of the slow relaxation mode δ (end-over-end rotation), whereas the latter to that of the fast relaxation mode α (rotation about the long axis).

Conclusion: ITZ glasses prepared by different cooling rates have very different structures, with faster cooling leading to lower (zero) smectic order, less regular lateral packing, and larger molecular spacings. The different structures can be characterized by two fictive temperatures, the higher one related to the regularity of smectic and lateral packing and the lower one to molecular spacings and enthalpy. The difference between the two fictive temperatures is as large as 20 K. Our results indicate that the interlayer and intralayer order in a smectic structure rise and fall together as part of liquid crystallinity, whereas the structural features associated with the nearest-neighbor environment can actively evolve even when the LC framework is frozen. At each cooling rate, the two fictive temperatures correspond to the glass transition temperatures for the two relaxation modes of ITZ observed by dielectric spectroscopy. The slower δ mode (end-over-end rotation) is associated with the freezing of the smectic and lateral-packing order and the faster α mode (axial rotation) with the freezing of molecular spacings and enthalpy. Our results indicate that the different aspects of glass structure can be manipulated independently.

References: Yu, J., Chen, Z., Teerakapibal, R., Benmore, C., Guzei, I., Richert, R., & Yu, L. (2022). Structure of Glasses with Tunable Liquid-crystalline Order by Cooling Rates. The Journal of Chemical Physics, 156(8):084504.

Acknowledgments: We thank the NSF (Grant No. DMR-1904601) for supporting this work and the NSF-supported University of Wisconsin Materials Research Science and Engineering Center (Grant No. DMR-1720415) for the use of its characterization facility.

Figure 1. Structure factors of ITZ glasses at 300 K prepared by cooling at 0.08 K/s (red) and 20 K/s (blue).



Figure 2. Measurement of the fictive temperatures of an ITZ glass relative to two features characterizing the lateral packing: (a) qL and (b) ξ. The glass was prepared by cooling at 20 K/s. In this experiment, it was heated while following qL and ξ. The fictive temperature is the intersection of the glass line and the liquid line. The two structural measures yield different Tf values.



Figure 3. Cooling rate effects on the fictive temperatures Tf of ITZ glasses. For each glass, Tf has been determined relative to six of its properties. Two groups of Tf values are observed, indicating two timescales are involved in the kinetic arrest. The regularity of smectic layers and lateral packing is frozen at a higher temperature than the molecular spacings between smectic layers and within each layer as well as the enthalpy of the system.