No abstract

At terahertz frequencies, the libration-vibration motions couple to the dielectric relaxations in disordered hydrogen-bonded solids. The interplay between these processes is still poorly understood, in particular at temperatures below the glass transition temperature, Tg, yet this behavior is of vital importance for the molecular mobility of such materials to remain in the amorphous phase. A series of polyhydric alcohols were studied at temperatures between 80 and 310 K in the frequency range of 0.2-3 THz using terahertz time-domain spectroscopy. Three universal features were observed in the dielectric losses, ϵ″(ν): (a) At temperatures well below the glass transition, ϵ″(ν) comprises a temperature-independent microscopic peak, which persists into the liquid phase and which is identified as being due to librational/torsional modes. For 0.65 Tg < T < Tg, additional thermally dependent contributions are observed, and we found strong evidence for its relation to the Johari-Goldstein secondary β-relaxation process. (b) Clear spectroscopic evidence is found for a secondary β glass transition at 0.65 Tg, which is not related to the fragility of the glasses. (c) At temperatures above Tg, the losses become dominated by primary α-relaxation processes. Our results show that the thermal changes in the losses seem to be underpinned by a universal change in the hydrogen bonding structure of the samples.

There is a controversy about the extent to which the primary and secondary dielectric relaxations influence the crystallization of amorphous organic compounds below the glass transition temperature. Recent studies also point to the importance of fast molecular dynamics on picosecond-to-nanosecond time scales with respect to the glass stability. In the present study we provide terahertz spectroscopy evidence on the crystallization of amorphous naproxen well below its glass transition temperature and confirm the direct role of Johari-Goldstein (JG) secondary relaxation as a facilitator of the crystallization. We determine the onset temperature Tβ above which the JG relaxation contributes to the fast molecular dynamics and analytically quantify the level of this contribution. We then show there is a strong correlation between the increase in the fast molecular dynamics and onset of crystallization in several chosen amorphous drugs. We believe that this technique has immediate applications to quantify the stability of amorphous drug materials.

Split-ring resonators represent the ideal route to achieve optical control of the incident light at THz frequencies. These subwavelength metamaterial elements exhibit broad resonances that can be easily tuned lithographically. We have realized a design based on the interplay between the resonances of metallic split rings and the electronic properties of monolayer graphene integrated in a single device. By varying the major carrier concentration of graphene, an active modulation of the optical intensity was achieved in the frequency range between 2.2 and 3.1 THz, achieving a maximum modulation depth of 18%, with a bias as low as 0.5 V.

Despite much effort in the area, no comprehensive understanding of the formation and behaviour of amorphous solids has yet been achieved. This severely limits the industrial application of such materials, including drug delivery where, in principle, amorphous solids have demonstrated their great usefulness in increasing the bioavailability of poorly aqueous soluble active pharmaceutical ingredients. Terahertz time-domain spectroscopy is a relatively novel analytical technique that can be used to measure the fast molecular dynamics of molecules with high accuracy in a non-contact and non-destructive fashion. Over the past decade a number of applications for the characterisation of amorphous drug molecules and formulations have been developed and it has been demonstrated how this technique can be used to determine the onset and strength in molecular mobility that underpins the crystallisation of amorphous drugs. In this review we provide an overview of the history, fundamentals and future perspective of pharmaceutical applications related to the terahertz dynamics of amorphous systems.