Using density changes to monitor blending with magnesium stearate by terahertz time-domain spectroscopy.

Magnesium stearate (MgSt) is among the most common excipients and the most common lubricant in solid oral products. It is primarily added to tablet formulations to ease ejection during tablet compression. While commonly present in low concentrations, the addition of MgSt substantially affects the final tablet properties.

THz-TDS transflection measurements as a process analyser for tablet mass.

Tablet content and content uniformity are essential for the market release of the drug product. For tablets, content and uniformity are determined by the weight ratio of active pharmaceutical ingredient in the tablet and the tablets' total mass. Novel process analytical technology tools for the control of the ratio of the active pharmaceutical ingredient have been proposed and implemented, but more robust, sensitive, and fast sensors for the control of tablet mass are desirable.

THz-TDS as a PAT tool for monitoring blend homogeneity in pharmaceutical manufacturing of solid oral dosage forms: A proof-of-concept study.

The process analytical technology (PAT) framework is well established and integral to facilitate process understanding, enable a transition from batch to continuous manufacturing, and improve product quality. Near-infrared (NIR) spectroscopy has been established as a standard PAT tool for many process analytical challenges, including monitoring powder blend homogeneity. However, alternative technologies for monitoring powder blending are of interest due to the importance of the blending step in manufacturing solid oral dosage forms.

Dynamical Transition in Dehydrated Proteins.

Terahertz time-domain spectroscopy and differential scanning calorimetry were used to study the role of the dynamics of biomolecules decoupled from solvent effects. Lyophilized sucrose exhibited steadily increasing absorption with temperature as anharmonic excitations commenced as the system emerged from a deep minimum of the potential energy landscape where harmonic vibrations dominate. The polypeptide bacitracin and two globular proteins, lysozyme and human serum albumin, showed a more complex temperature dependence.

Towards simultaneous determination of tablet porosity and height by terahertz time-domain reflection spectroscopy.

The quality control of pharmaceutical tablets is still based on testing small sample numbers using at- and off-line testing methods. Traditional in-process controls, such as tablet mass, height, mechanical strength, and disintegration time are time- and resource-consuming and poorly suited to support an effective transition towards continuous manufacturing. Another suitable parameter to monitor during production would be tablet porosity.

Terahertz time-domain spectroscopy for the investigation of tablets prepared from roller compacted granules.

Roller compaction before tableting is a common unit operation to increase the processability of powders. Terahertz time-domain spectroscopy (THz-TDS) has recently been introduced as a potential process analytical technology (PAT) for measuring tablet porosity based on the refractive index of the tablet. Tablet porosity is a governing parameter for tablet disintegration and dissolution.

The effect of mAb and excipient cryoconcentration on long-term frozen storage stability - Part 1: Higher molecular weight species and subvisible particle formation.

Cryoconcentration upon large-scale freezing of monoclonal antibody (mAb) solutions leads to regions of different ratios of low molecular weight excipients, like buffer species or sugars, to protein. This study focused on the impact of the buffer species to mAb ratio on aggregate formation after frozen storage at -80 °C, -20 °C, and - 10 °C after 6 weeks, 6 months, and 12 months. An optimised sample preparation was established to measure T' of samples with different mAb to histidine ratios via differential scanning calorimetry (DSC).

Terahertz time-domain spectroscopy for powder compact porosity and pore shape measurements: An error analysis of the anisotropic bruggeman model.

Terahertz time-domain spectroscopy (THz-TDS) is a novel technique which has been applied for pore structure analysis and porosity measurements. For this, mainly the anisotropic Bruggeman (AB-EMA) model is applied to correlate the effective refractive index ( ) of a tablet and the porosity as well as to evaluate the pore shape based on the depolarisation factor . This paper investigates possible error sources of the AB-EMA for THz-TDS based tablet analysis.

Non-destructive quantification of fragmentation within tablets after compression from scattering analysis of terahertz transmission measurements.

Material deformation behaviour has a critical impact on tablet formation. Fragmentation is one of the key mechanisms affecting the strength of a final compact, however, quantitative methods for estimating fragmentation are often complex, destructive and time-consuming. The purpose of this study was to investigate the applicability of terahertz time-domain spectroscopy (THz-TDS) to quantify fragmentation upon tableting.