Pharmaceutical Terahertz Spectroscopy and Imaging

Zeitler, J. Axel

doi:10.1007/978-1-4939-4029-5_5

Cited by 30 publications

(21 citation statements)

References 159 publications

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“…Besides these advantages the terahertz method is capable of detecting not only minute changes in the physical structure of the tablet matrix but also changes in the chemical composition. If inhomogeneities in the powder or granule mixture develop during the process run this can be picked up not only by the subtle changes in relative refractive index but directly in the absorption data as spectral changes [9]. The method is in principle capable to ensure content uniformity as well as provide predictions for the tablet disintegration.…”

Section: Resultsmentioning

confidence: 99%

“…By assuming the tablet as a homogeneous medium, the frequency-dependent effective refractive index and the effective absorption coefficient can be determined by combining the transmission spectrum, Beer-Lambert’s law and the measured tablet thickness. More details about the extraction of optical constants from terahertz measurements is provided by Zeitler [9]. …”

Section: Methodsmentioning

confidence: 99%

“…Together with the non-ionising nature of terahertz radiation as well as the short measurement time (milliseconds) this technology could provide a potential process analytical technology (PAT) tool to non-destructively characterise pharmaceutical tablets, e.g. , coating structures, porosity, hardness and density [9]. …”

Section: Introductionmentioning

confidence: 99%

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Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements

Markl

Sauerwein

Goodwin³

et al. 2017

Pharm Res

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PurposeThe aim of this study was to establish the suitability of terahertz (THz) transmission measurements to accurately measure and predict the critical quality attributes of disintegration time and the amount of active pharmaceutical ingredient (API) dissolved after 15, 20 and 25 min for commercial tablets processed at production scale.MethodsSamples of 18 batches of biconvex tablets from a production-scale design of experiments study into exploring the design space of a commercial tablet manufacturing process were used. The tablet production involved the process steps of high-shear wet granulation, fluid-bed drying and subsequent compaction. The 18 batches were produced using a 4 factor split plot design to study the effects of process changes on the disintegration time. Non-destructive and contactless terahertz transmission measurements of the whole tablets without prior sample preparation were performed to measure the effective refractive index and absorption coefficient of 6 tablets per batch.ResultsThe disintegration time (R 2 = 0.86) and API dissolved after 15 min (R 2 = 0.96) linearly correlates with the effective refractive index, n eff, measured at terahertz frequencies. In contrast, no such correlation could be established from conventional hardness measurements. The magnitude of n eff represents the optical density of the sample and thus it reflects both changes in tablet porosity as well as granule density. For the absorption coefficient, α eff, we observed a better correlation with dissolution after 20 min (R 2 = 0.96) and a weaker correlation with disintegration (R 2 = 0.83) compared to n eff.ConclusionThe measurements of n eff and α eff provide promising predictors for the disintegration and dissolution time of tablets. The high penetration power of terahertz radiation makes it possible to sample a significant volume proportion of a tablet without any prior sample preparation. Together with the short measurement time (seconds), the potential to measure content uniformity and the fact that the method requires no chemometric models this technology shows clear promise to be established as a process analyser to non-destructively predict critical quality attributes of tablets.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-017-2108-4) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements

Markl

Sauerwein

Goodwin³

et al. 2017

Pharm Res

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“…The frequency-domain analysis of the refractive index may provide additional information about the sample, such as specific phonon vibrations due to a crystalline constituent (e.g. the drug) in the sample (Zeitler, 2016). Such spectral features cause relatively strong dispersion and the refractive index thus undergoes substantial changes at the frequencies of these features.…”

Section: Measurement Of Total Porositymentioning

confidence: 99%

Characterisation of pore structures of pharmaceutical tablets: A review

Markl

Strobel

Schlossnikl

et al. 2018

International Journal of Pharmaceutics

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108

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Traditionally, the development of a new solid dosage form is formulation-driven and less focus is put on the design of a specific microstructure for the drug delivery system. However, the compaction process particularly impacts the microstructure, or more precisely, the pore architecture in a pharmaceutical tablet. Besides the formulation, the pore structure is a major contributor to the overall performance of oral solid dosage forms as it directly affects the liquid uptake rate, which is the very first step of the dissolution process. In future, additive manufacturing is a potential game changer to design the inner structures and realise a tailor-made pore structure. In pharmaceutical development the pore structure is most commonly only described by the total porosity of the tablet matrix. Yet it is of great importance to consider other parameters to fully resolve the interplay between microstructure and dosage form performance. Specifically, tortuosity, connectivity, as well as pore shape, size and orientation all impact the flow paths and play an important role in describing the fluid flow in a pharmaceutical tablet. This review presents the key properties of the pore structures in solid dosage forms and it discusses how to measure these properties. In particular, the principles, advantages and limitations of helium pycnometry, mercury porosimetry, terahertz time-domain spectroscopy, nuclear magnetic resonance and X-ray computed microtomography are discussed.

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“…An alternative to XμCT is terahertz pulsed imaging (TPI) allowing for the acquisition of single depth-resolved scans in a few milliseconds. TPI is a novel modality for physical characterization of pharmaceutical drug materials and solid dosage forms (21). Terahertz radiation easily penetrates through most polymeric materials (22) making it an attractive tool for non-destructive testing of pharmaceutical products.…”

Section: Introductionmentioning

confidence: 99%

Analysis of 3D Prints by X-ray Computed Microtomography and Terahertz Pulsed Imaging

et al. 2016

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PurposeA 3D printer was used to realise compartmental dosage forms containing multiple active pharmaceutical ingredient (API) formulations. This work demonstrates the microstructural characterisation of 3D printed solid dosage forms using X-ray computed microtomography (XμCT) and terahertz pulsed imaging (TPI).MethodsPrinting was performed with either polyvinyl alcohol (PVA) or polylactic acid (PLA). The structures were examined by XμCT and TPI. Liquid self-nanoemulsifying drug delivery system (SNEDDS) formulations containing saquinavir and halofantrine were incorporated into the 3D printed compartmentalised structures and in vitro drug release determined.ResultsA clear difference in terms of pore structure between PVA and PLA prints was observed by extracting the porosity (5.5% for PVA and 0.2% for PLA prints), pore length and pore volume from the XμCT data. The print resolution and accuracy was characterised by XμCT and TPI on the basis of the computer-aided design (CAD) models of the dosage form (compartmentalised PVA structures were 7.5 ± 0.75% larger than designed; n = 3).ConclusionsThe 3D printer can reproduce specific structures very accurately, whereas the 3D prints can deviate from the designed model. The microstructural information extracted by XμCT and TPI will assist to gain a better understanding about the performance of 3D printed dosage forms.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-016-2083-1) contains supplementary material, which is available to authorized users.

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Pharmaceutical Terahertz Spectroscopy and Imaging

Cited by 30 publications

References 159 publications

Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements

Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements

Characterisation of pore structures of pharmaceutical tablets: A review

Analysis of 3D Prints by X-ray Computed Microtomography and Terahertz Pulsed Imaging

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