Impact of Processing Conditions on Inter-tablet Coating Thickness Variations Measured by Terahertz In-Line Sensing.

A novel in-line technique utilising pulsed terahertz radiation for direct measurement of the film coating thickness of individual tablets during the coating process was previously developed and demonstrated on a production-scale coater. Here, we use this technique to monitor the evolution of tablet film coating thickness and its inter-tablet variability during the coating process under a number of different process conditions that have been purposefully induced in the production-scale coating process. The changes that were introduced to the coating process include removing the baffles from the coater, adding uncoated tablets to the running process, halting the drum, blockage of spray guns and changes to the spray rate. The terahertz sensor was able to pick up the resulting changes in average coating thickness in the coating drum and we report the impact of these process changes on the resulting coating quality.

Systematic study of terahertz time-domain spectra of historically informed black inks.

The potential of terahertz-time domain spectroscopy (THz-TDS) as a diagnostic tool for studies of inks in historical documents is investigated in this paper. Transmission mode THz-TDS was performed on historically informed model writing and drawing inks. Carbon black, bistre and sepia inks show featureless spectra between 5 and 75 cm(-1) (0.15-2.25 THz); however, their analysis still provided useful information on the interaction of terahertz radiation with amorphous materials. On the other hand, THz-TDS can be used to distinguish different iron gall inks with respect to the amount of iron(II) sulfate contained, as sharp spectral features are observed for inks containing different ratios of iron(II) sulfate to tannic or gallic acid. Additionally, copper sulfate was found to modify the structure of iron(II) precipitate. Furthermore, Principal Component Analysis (PCA) applied to THz-TDS spectra, highlights changes in iron gall inks during thermal degradation, during which a decrease in the sharp spectral bands associated with iron(II) sulfate is observed. ATR-FTIR spectroscopy combined with THz-TDS of dynamically heated ink samples indicate that this phenomenon is due to dehydration of iron(II) sulfate heptahydrate. While this research demonstrates the potential of THz-TDS to improve monitoring of the chemical state of historical documents, the outcomes go beyond the heritage field, as it also helps to develop the theoretical knowledge on interactions between terahertz radiation and matter, particularly in studies of long-range symmetry (polymorphism) in complex molecular structures and the role played by the surrounding matrix, and also indicates the potential of THz-TDS for the optimization of contrast in terahertz imaging.

Hardness and density distributions of pharmaceutical tablets measured by terahertz pulsed imaging.

We present terahertz pulsed imaging (TPI) as a novel tool to quantify the hardness and surface density distribution of pharmaceutical tablets. Good agreement between the surface refractive index (SRI) measured by TPI and the crushing force measured from diametral compression tests was found using a set of tablets that were compacted at various compression forces. We also found a strong correlation between TPI results and tablet bulk density, and how these relate to tablet hardness. Numerical simulations of tablet surface density distribution by finite element analysis exhibit excellent agreement with the TPI measured SRI maps. These results show that TPI has an advantage over traditional diametral compression and is more suitable for nondestructive hardness and density distribution monitoring and control of pharmaceutical manufacturing processes.

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.