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Terahertz Instrumentation for Research

Terahertz pulsed imaging provides an insight to disintegration failure in solid dosage form failure

Tablet disintegration is a property of products within the pharmaceutical industry that has been commonly investigated. The significance of disintegration lies in the availability of the active pharmaceutical ingredient (API) to be dissolved inside the body and reach the bloodstream to take effect. An up and coming approach for the analysis of tablet disintegration is terahertz pulsed imaging (TPI). TPI is a quick, efficient technique to perform these measurements.

Terahertz Pulsed Imaging

TPI functions on the principle of the terahertz beam reflection. The terahertz beam is focused onto a sample, some of the beam reflects from the surface, some penetrates the surface and reflects from various layers (and structures) within the sample, while some of the beam completely penetrates the sample and is lost out of the back. At each surface of reflection, the inherent time-delay of the terahertz radiation’s return to the sensor head can be used to identify the location (depth) of the layers and interfaces within the given sample. From this information, it is possible to determine properties such as layer thicknesses.

In the case of tablet disintegration, TPI can track the influx of a solvent into the sample under investigation. By treating the solvent front as another layer within the sample, TPI is capable of providing the depth of penetration of the solvent into the sample, in addition to the timeline.

TeraView TeraPulse 4000 with PolyScan Head

TeraView’s TeraPulse 4000 system has world-leading signal-to-noise, bandwidth and modular extension options to meet the challenging research needs. With systems installed in over 25 countries worldwide, TeraView’s expertise in terahertz instrumentation and pioneering applications work is unmatched among vendors, and this knowledge and experience have been used in the design of the TeraPulse 4000.

Four fibre points are available to support such external fibres, bespoke probes for in-line or other industrial applications, as well as internal or external sample chamber which accepts TeraView’s wide range of accessories.

It is possible to configure the system to meet the challenging requirements.

Key features include:

  • Frequency coverage from 0.06 THz to typically 4.5 THz from a single emitter; extendable to 6 THz.
  • Excellent spectral resolution of 1.7 GHz, but typically can achieve 1 GHz as standard with no recalibration of optical delay required.
  • Single laser system and therefore, low jitter between emitter and receiver beams allowing detection of layers as thin as 20 µm.
  • Wide range of plug and play modules for easy and cost-efficient extension of the capabilities of the instrument.
  • Short warm-up time; no need for calibration of an electronic delay line.
  • Uninterrupted use of the instrument during data acquisition.

Multiple fiber ports (optional 030-9501) enable the use of fiber probes and plug and play modules without the two experimental configurations interfering with each other.

PolyScan Sensor Head

The TeraPulse 4000 can be offered with the PolyScan head option. This option has a length of optical fibres extending out of the TeraPulse core unit. The terahertz sensor head is attached at the end of the fibres and can be used for various measurements. The PolyScan allows for a lot of placement options including, attachment to moving gantries, movable set-ups, stationary set-ups, etc.

PolyScan heads give terahertz data based on the reflections of the terahertz signal from the various interfaces of the object being investigated.

Experimental

The use of TPI to examine the disintegration of pharmaceutical tablets has been garnering a lot of interest recently. In order to perform this measurement, the sample has to be placed in such a way that one side faces the terahertz emitter/detector and the other side is in contact with a solvent. The terahertz pulses are directed at the sample, which gives the reflection data from the layer(s) present. Once the solvent starts to penetrate into the sample, the newly created reflection(s) can be detected and interpreted to establish the penetration depth of the solvent. The image below shows the design of the disintegration measurements.1

These measurements do not directly provide the disintegration information, but after designing and performing a set of calibration-like measurements, it is possible to correlate the disintegration properties to the solvent ingress rates for the samples.

Results and Discussion

In a recent publication1, the effects of disintegration on microcrystalline cellulose (MCC) were investigated. In order to prepare the MCC, lactose powder was compacted into a sample tablet of 1.5 mm thickness. The TPI experimental data was collected using the aforementioned setup. The timeframe of this experiment proved to be very short, as the solvent broke through the front side of the MCC tablet in a matter of 23 seconds. The image below shows the waveforms acquired throughout the 23 second window.

The two peaks present in all of these spectra arise from the front (0 mm) and back (~2 mm) sides of the lactose tablet. As time progressed from 0 to 23 seconds, a third peak, belonging to the solvent, is determined and shifts from 2 mm to 0 mm. This series of spectra illustrates the TPI’s capability to identify the ingress of a solvent into a tablet sample. This data gives the penetration depth of the solvent. By collecting the data from these measurements of the solvent ingress and systematically changing the properties of the tablets, disintegration times for the components being investigated can be predicted using the data.

Conclusions

Recent work has demonstrated that terahertz pulsed imaging is an effective method for investigating solvent ingress into pharmaceutical ingredients. It has also been shown that by using the data collected from these measurements, the disintegration times of the compounds being investigated can be derived.

References

Zeitler, J. A., Pharmaceutical Terahertz Spectroscopy and Imaging. ResearchGate. Chapter. 2016. 1-53.

An international research team has upgraded an imaging method able to unveil, in high-resolution 3D, the structure of layers below the surface of paintings and other objects, opening up new prospects for art-history investigations—and much more.

The full article can be read on the CNRS News website here.