The significance of the amorphous potential energy landscape for dictating glassy dynamics and driving solid-state crystallisation.

The fundamental origins surrounding the dynamics of disordered solids near their characteristic glass transitions continue to be fiercely debated, even though a vast number of materials can form amorphous solids, including small-molecule organic, inorganic, covalent, metallic, and even large biological systems. The glass-transition temperature, T, can be readily detected by a diverse set of techniques, but given that these measurement modalities probe vastly different processes, there has been significant debate regarding the question of why T can be detected across all of them. Here we show clear experimental and computational evidence in support of a theory that proposes that the shape and structure of the potential-energy surface (PES) is the fundamental factor underlying the glass-transition processes, regardless of the frequency that experimental methods probe.

Quantification of cation-anion interactions in crystalline monopotassium and monosodium glutamate salts.

Crystalline salt compounds composed of metal cations and organic anions are becoming increasingly popular in a number of fields, including the pharmaceutical and food industries, where such formulations can lead to increased product solubility. The origins of these effects are often in the interactions between the individual components in the crystals, and understanding these forces is paramount for the design and utilisation of such materials. Monosodium glutamate monohydrate and monopotassium glutamate monohydrate are two solids that form significantly different structures with correspondingly dissimilar dynamics, while their chemistry only differs in cation identity.

A comprehensive spectroscopic study of the polymorphs of diflunisal and their phase transformations.

Understanding phase transitions in pharmaceutical materials is of vital importance for drug manufacturing, processing and storage. In this paper we have carried out comprehensive high-resolution spectroscopic studies on the polymorphs of the non-steroidal anti-inflammatory drug diflunisal that has four known polymorphs, forms I-IV (FI-FIV), three of which have known crystal structures. Phase transformations during milling, heating, melt-quenching and exposure to high relative humidity were investigated using Raman and terahertz spectroscopy in combination with differential scanning calorimetry and X-ray powder diffraction.

Examination of l-Glutamic Acid Polymorphs by Solid-State Density Functional Theory and Terahertz Spectroscopy.

The ability of l-glutamic acid to crystallize in two different forms has long been the subject of study due to its commercial importance. While a solvent-mediated phase transformation between the α and β polymorphs is the prevailing theory, recent reports indicate a thermal solid-solid transformation between the two may be possible. However, determining accurate thermodynamic stabilities of these crystals has been challenging.

(19) F NMR Spectroscopy as a Highly Sensitive Method for the Direct Monitoring of Confined Crystallization within Nanoporous Materials.

The introduction of fluorine into the structure of pharmaceuticals has been an effective strategy for tuning their pharmacodynamic properties, with more than 40 new drugs entering the market in the last 15 years. In this context, (19) F NMR spectroscopy can be viewed as a useful method for investigating the host-guest chemistry of pharmaceuticals in nanosized drug-delivery systems. Although the interest in confined crystallization, nanosized devices, and porous catalysts is gradually increasing, understanding of the complex phase behavior of organic molecules confined within nanochambers or nanoreactors is still lacking.

Measuring the Elasticity of Poly-l-Proline Helices with Terahertz Spectroscopy.

The rigidity of poly-l-proline is an important contributor to the stability of many protein secondary structures, where it has been shown to strongly influence bulk flexibility. The experimental Young's moduli of two known poly-l-proline helical forms, right-handed all-cis (Form I) and left-handed all-trans (Form II), were determined in the crystalline state by using an approach that combines terahertz time-domain spectroscopy, X-ray diffraction, and solid-state density functional theory. Contrary to expectations, the helices were found to be considerably less rigid than many other natural and synthetic polymers, as well as differing greatly from each other, with Young's moduli of 4.

Direct measurement of molecular mobility and crystallisation of amorphous pharmaceuticals using terahertz spectroscopy.

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.

The Disintegration Process in Microcrystalline Cellulose Based Tablets, Part 1: Influence of Temperature, Porosity and Superdisintegrants.

Disintegration performance was measured by analysing both water ingress and tablet swelling of pure microcrystalline cellulose (MCC) and in mixture with croscarmellose sodium using terahertz pulsed imaging (TPI). Tablets made from pure MCC with porosities of 10% and 15% showed similar swelling and transport kinetics: within the first 15s, tablets had swollen by up to 33% of their original thickness and water had fully penetrated the tablet following Darcy flow kinetics. In contrast, MCC tablets with a porosity of 5% exhibited much slower transport kinetics, with swelling to only 17% of their original thickness and full water penetration reached after 100s, dominated by case II transport kinetics.

Predicting Crystallization of Amorphous Drugs with Terahertz Spectroscopy.

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.

The Disintegration Process in Microcrystalline Cellulose Based Tablets, Part 1: Influence of Temperature, Porosity and Superdisintegrants.

Disintegration performance was measured by analysing both water ingress and tablet swelling of pure microcrystalline cellulose (MCC) and in mixture with croscarmellose sodium using terahertz pulsed imaging (TPI). Tablets made from pure MCC with porosities of 10% and 15% showed similar swelling and transport kinetics: within the first 15 s, tablets had swollen by up to 33% of their original thickness and water had fully penetrated the tablet following Darcy flow kinetics. In contrast, MCC tablets with a porosity of 5% exhibited much slower transport kinetics, with swelling to only 17% of their original thickness and full water penetration reached after 100 s, dominated by case II transport kinetics.

Thermal Decoupling of Molecular-Relaxation Processes from the Vibrational Density of States at Terahertz Frequencies in Supercooled Hydrogen-Bonded Liquids.

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.

Crystallization and phase changes in paracetamol from the amorphous solid to the liquid phase.

For the case of paracetamol, we show how terahertz time-domain spectroscopy can be used to characterize the solid and liquid phase dynamics. Heating of supercooled amorphous paracetamol from 295 K in a covered sample under vacuum leads to its crystallization at 330 K. First, form III is formed followed by the transformation of form III to form II at 375 K, to form I at 405 K, and finally melting is observed around 455 K.

Low-bias terahertz amplitude modulator based on split-ring resonators and graphene.

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.

Glassy dynamics of sorbitol solutions at terahertz frequencies.

The absorption spectra of D-sorbitol and a range of its concentrated aqueous solutions were studied by terahertz spectroscopy over the temperature interval of 80 K < T < 310 K. It is shown that the slow-down of molecules at around the glass transition temperature, Tg, dramatically influences the thermal dependence of the absorption at terahertz frequencies. Furthermore, two different absorption regimes are revealed below Tg: at temperatures well below Tg, the absorption resembles the coupling of terahertz radiation to the vibrational density of states (VDOS); above these temperatures, between 160 K and Tg, in the sample of pure sorbitol and the sample of a solution of 70 wt% sorbitol in water, another type of absorption is observed at terahertz frequencies.