J. Axel Zeitler

Tuning the acid/base properties of nanocarbons by functionalization via amination

The surface chemical properties and the electronic properties of vapor grown carbon nanofibers (VGCNFs) have been modified by treatment of the oxidized CNFs with NH(3). The effect of treatment temperature on the types of nitrogen functionalities introduced was evaluated by synchrotron based X-ray photoelectron spectroscopy (XPS), while the impact of the preparation methods on the surface acid-base properties was investigated by potentiometric titration, microcalorimetry, and zeta potential measurements. The impact of the N-functionalization on the electronic properties was measured by THz-Time Domain spectroscopy. The samples functionalized via amination are characterized by the coexistence of acidic and basic O and N sites. The population of O and N species is temperature dependent. In particular, at 873 K nitrogen is stabilized in substitutional positions within the graphitic structure, as heterocyclic-like moieties. The surface presents heterogeneously distributed and energetically different basic sites. A small amount of strong basic sites gives rise to a differential heat of CO(2) adsorption of 150 kJ mol(-1). However, when functionalization is carried out at 473 K, nitrogen moieties with basic character are introduced and the maximum heat of adsorption is significantly lower, at approximately 90 kJ mol(-1). In the latter sample, energetically different basic sites coexist with acidic oxygen groups introduced during the oxidative step. Under these conditions, a bifunctional acidic and basic surface is obtained with high hydrophilic character. N-functionalization carried out at higher temperature changes the electronic properties of the CNFs as evaluated by THz-TDS. The functionalization procedure presented in this work allows high versatility and flexibility in tailoring the surface chemistry of nanocarbon material to specific needs. This work shows the potential of the N-containing nanocarbon materials obtained via amination in catalysis as well as electronic device materials.

Terahertz pulsed spectroscopy and imaging in the pharmaceutical setting--a review.

Terahertz pulsed spectroscopy (TPS) and terahertz pulsed imaging (TPI) are two novel techniques for the physical characterization of pharmaceutical drug materials and final solid dosage forms, utilizing spectral information in the far infrared region of the electromagnetic spectrum. This review focuses on the development and performance of pharmaceutical applications of terahertz technology compared with other tools for physical characterization. TPS can be used to characterize crystalline properties of drugs and excipients. Different polymorphic forms of a drug can be readily distinguished and quantified. Recent developments towards a better understanding of the fundamental theory behind spectroscopy in the far infrared have been discussed. Applications for TPI include the measurement of coating thickness and uniformity in coated pharmaceutical tablets, structural imaging and 3D chemical imaging of solid dosage forms.

Terahertz In-Line Sensor for Direct Coating Thickness Measurement of Individual Tablets During Film Coating in Real-Time

We present a new in-line measurement technique to determine the coating thickness of individual pharmaceutical tablets during film coating in a pan coating unit using pulsed terahertz technology. Results of these real-time terahertz measurements acquired during a production scale coating run are validated using both off-line high-resolution terahertz pulsed imaging of the whole dosage form as well as weight-gain measurements made on sample tablets removed at discrete time intervals during the process run. The terahertz measurements provide a direct method of determining the coating thickness, and no chemometric calibration models are required for the quantification. The results, and their repeatability, demonstrate that real-time monitoring of pharmaceutical tablet coating is not only possible but also provides substantially more information of the coating quality than the standard quality control method. Rather than providing the average coating thickness of a large number of tablets, the terahertz sensor provides the thickness of up to 100 individual tablet coatings per minute. Using this information, the operator can get additional information about the thickness distribution in the coating pan and adjust the process accordingly. At present, a minimum coating thickness of 40 μm is required to determine the coating thickness. The technique is applicable for coatings up to 1 mm in thickness. Within that range, it provides thickness measurements of sub-micron resolution. Terahertz in-line coating process measurements show considerable potential for applications in real-time release, process analytical technology and quality by design.

Applications of terahertz pulsed imaging to sustained-release tablet film coating quality assessment and dissolution performance

The potential of terahertz pulsed imaging (TPI) to predict the dissolution performance in sustained-release tablets was investigated in this study. Batches of coated tablets with similar weight gain during the coating process at the lab and pilot scales were subjected to non-destructive imaging by TPI and subsequently analysed by dissolution testing. The results from the dissolution tests revealed significant differences in the product performance between the lab and pilot scales (Student t-test, P<0.05). The model-independent dissolution parameters in the pilot scale showed a prolonged mean dissolution time. This indicated that the pharmaceutical active ingredient was released at a slower rate in the pilot compared to the lab scale. While weight gain measurements (the traditional coating quality parameter), failed to provide an early indication of the product functional performance; terahertz parameters (terahertz electric field peak strength and coating layer thickness) provided insight into the subsequent dissolution behaviour. Correlations between terahertz parameters and dissolution were much stronger than correlations between weight gain and dissolution; with the R(2) value for terahertz correlations typically around 0.84 as opposed to 0.07 for weight gain correlations. This study presents the initial finding of correlations between terahertz parameters for assessing the coating quality to the dissolution performance of the coated tablet. The contributing factors for these particular correlations are also discussed.

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. 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.

Direct evidence to support the restriction of intramolecular rotation hypothesis for the mechanism of aggregation-induced emission: temperature resolved terahertz spectra of tetraphenylethene

In contrast to the traditional fluorescent dyes that exhibit a decrease in fluorescence upon aggregation, Aggregation-Induced Emission (AIE) molecules are a family of fluorophors which exhibit increased fluorescence upon aggregation. Consequently, AIE molecules represent an interesting new material with potential applications in fluorescent chemo/biosensors, light emitting devices and medical diagnostics. Numerous mechanisms have been proposed to explain this phenomenon, including E–Z isomerization, and restriction of intramolecular rotations (RIR). However, there has not been any direct experimental evidence to support either one of these hypotheses. Here we use terahertz time-domain-spectroscopy (THz-TDS) and solid-state computational simulations of an AIE molecule to link the increase in intensity of intramolecular rotation and rocking modes to the measured fluorescence and reveal direct evidence supporting the RIR hypothesis. This is the first time that terahertz spectroscopy has been used to directly probe such molecular motions in AIE materials and in doing so we have found conclusive evidence to fully explain the AIE mechanism.

A study into the effect of subtle structural details and disorder on the terahertz spectrum of crystalline benzoic acid

The phonon modes of crystalline benzoic acid have been investigated using terahertz time-domain spectroscopy, rigid molecule atom-atom model potential and plane-wave density functional theory lattice dynamics calculations. The simulation results show good agreement with the measured terahertz spectra and an assignment of the terahertz absorption features of benzoic acid is made with the help of both computational methods. Focussing on the strongest interactions in the crystal, we describe each vibration in terms of distortions of the benzoic acid hydrogen bonded dimers that are present in the crystal structure. The terahertz spectrum is also shown to be highly sensitive to the location of the carboxylic acid hydrogen atoms in the cyclic hydrogen-bonded dimers and we have systematically explored the influence of the observed disorder in the hydrogen atom positions on the lattice dynamics.

Terahertz time-domain and low-frequency Raman spectroscopy of organic materials.

With the ongoing proliferation of terahertz time-domain instrumentation from semiconductor physics into applied spectroscopy over the past decade, measurements at terahertz frequencies (1 THz ≡ 1012 Hz ≡ 33 cm–1) have attracted a sustained growing interest, in particular the investigation of hydrogen-bonding interactions in organic materials. More recently, the availability of Raman spectrometers that are readily able to measure in the equivalent spectral region very close to the elastic scattering background has also grown significantly. This development has led to renewed efforts in performing spectroscopy at the interface between dielectric relaxation phenomena and vibrational spectroscopy. In this review, we briefly outline the underlying technology, the physical phenomena governing the light–matter interaction at terahertz frequencies, recent examples of spectroscopic studies, and the current state of the art in assigning spectral features to vibrational modes based on computational techniques.

The influence of various excipients on the conversion kinetics of carbamazepine polymorphs in aqueous suspension.

The influence of various excipients on the conversion of carbamazepine polymorphs to the dihydrate in aqueous suspension has been investigated. Ten excipients having functional groups which were potentially able to form hydrogen bonds with carbamazepine (group 1: methylcellulose, hypromellose (hydroxypropyl methylcellulose), hydroxypropylcellulose (HPC), 2‐hydroxyethylcellulose (HEC), carmellose sodium (sodium carboxymethylcellulose), cellobiose; group 2: povidone (polyvinylpyrrolidone), povidone‐vinyl acetate copolymer (povidone/VA) and N‐methyl‐2‐pyrrolidone; group 3: macrogol (polyethylene glycol) and polyethylene oxide‐polypropylene oxide copolymer (PEO/PPO)) were selected. Carbamazepine polymorphic forms III and I were dispersed separately into each aqueous excipient solution (0.1%, w/v) for 30 min at room temperature. The inhibition effect of each excipient was quantified using Raman spectroscopy combined with multivariate analyses. The solubility parameter of each excipient was calculated and used for categorizing excipients. Excipients in groups 1 and 2, which had both low solubility parameters (< 27.0 MPa½) and strong hydrogen bonding groups, inhibited the conversion completely. With increasing solubility parameter, the inhibition effect decreased for group 1 excipients, especially for carbamazepine form I, which had a higher specific surface area. Also, the excipients of group 3, lacking strong hydrogen bonding groups, showed poor inhibition although they had low solubility parameters (< 21.0 MPa½). This study indicated the importance of both hydrogen bonding interaction and a suitable hydrophobicity (expressed by the solubility parameter) in the inhibition of the conversion of carbamazepine to the dihydrate.

Prediction of dissolution time and coating thickness of sustained release formulations using Raman spectroscopy and terahertz pulsed imaging

Raman spectroscopy was implemented successfully as a non-invasive and rapid process analytical technology (PAT) tool for in-line quantitative monitoring of functional coating. Coating experiments were performed at which diprophylline tablets were coated with a sustained release formulation based on Kollicoat SR 30 D. Using PLS a multivariate model was constructed by correlating Raman spectral data with the mean dissolution time as determined by dissolution testing and the coating thickness as measured by terahertz pulsed imaging. By performing in-line measurements it was possible to monitor the progress of the coating process and to detect the end point of the process, where the acquired coating amount was achieved for the desired MDT or coating thickness.