Introduction
Many recent studies have given focus to amorphous active pharmaceutical ingredients (APIs). In most cases, the amorphous form facilitates greater bioavailability of the API. Studies have been conducted to gain further knowledge on the transitions and stabilities of amorphous APIs. The dynamics of amorphous APIs have been traditionally investigated using methods such as inelastic neutron scattering and dielectric spectroscopy. However, these techniques are not only expensive, but also time intensive.
Terahertz Spectroscopy
Terahertz spectroscopy technique is non-destructive as well as non-ionizing, and is capable of penetrating non-conducting materials. It is a useful technique in many fields, including medical imaging, art preservation and pharmaceuticals.
In the studies of amorphous materials, the stabilities of amorphous APIs can be predicted using terahertz spectroscopy. Also, the underlying physical properties governing the stabilities of amorphous APIs can be further explored using this technique.
TeraView TeraPulse 4000 Terahertz Spectrometer
The TeraPulse 4000 terahertz spectrometer is a portable instrument that can perform both transmission and reflection measurements within a single box. The unit can be used along with all of TeraView's existing imaging and spectroscopy modules and accessories.
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The TeraPulse 4000 is TeraView's new spectrometer and imaging bench-top unit with a modular design, thus allowing all accessories to be fully used for reflection and transmission measurements. Equipped with TeraView's proprietary semiconductor based technology, the TeraPulse offers market leading signal to noise, with a quality signal up to 4 THz. The option of extending this beyond 7 THz also exists.
The TeraPulse’s modular design not only simplifies any maintenance, but also allows it to automatically accept/recognize the company’s extensive and unique range of accessories. Smooth operation of the unit is ensured by the newly developed software. Options are also available for the instrument to be integrated into a suitable industrial casing, making it to be compliant with IP65 and IP67 standards.
Experiment
Terahertz spectroscopy has traditionally been used to investigate crystalline materials due to the possibility of acquiring a unique spectrum for the molecular solid being studied. During the analysis of amorphous materials, the terahertz spectra are often observed like a rising, featureless absorption. More recently, this technique has been employed to investigate the dynamics, stability and how these two properties are linked in these amorphous APIs.
The rapid cooling of a liquid to a solid leads to the formation of amorphous APIs. During this process, fast-cooling dynamics allow for the system to avoid crystallization and become trapped in a disordered state, a glass. The temperature where this transition occurs is called the glass transition temperature, Tg. The temperatures higher and lower than Tg show differing rates for the changes in the dynamics. These relaxation dynamics are classified into two categories: lower-frequency alpha and higher frequency beta relaxation processes. The alpha relaxations represent intermolecular motions and the beta relaxations represent intramolecular motions. Temperature plays a key role in these relaxations and each of them has a glass transition temperature associated with it.
Results and Discussion
In a recent work, it has been demonstrated that terahertz spectroscopy can detect the glass transition temperatures and the rate at which the relaxation frequency modulates as a function of temperature. Moreover, a direct relationship has been established between the secondary Johari-Goldstein ß relaxation and the stability of amorphous APIs. In addition, data obtained from terahertz spectroscopy can reveal the dielectric loss in these materials which can be applied to determine the stabilities of amorphous materials.
