Terahertz sensing for pharmaceutical applications
Doktorsavhandling, 2023

Pharmaceutical tablets are manufactured through the compaction of powder blends or granules in batch or continuous processes. In continuous manufacturing, real-time assurance of quality becomes essential to ensure that the final product meets the quality standards approved by manufacturers and regulatory authorities. Process analytical methods used for real-time monitoring and control should be rapid, non-destructive, and suitable to be conducted in the manufacturing area. This thesis demonstrates the terahertz frequency domain (THz-FD) technique, based on all-electronic solutions, as a fast, sensitive, and non-destructive sensing technique, with the advantage of a reasonable compromise between deep penetration depth and high spatial resolution, high dynamic range, and miniaturization capabilities. In this study, the THz-FD technique was explored to monitor the key physical properties such as tablet density and porosity through effective refractive index using a vector network analyser. In addition, taking advantage of the lower scattering effect of the THz region compared to higher frequencies, the feasibility of terahertz frequency domain spectroscopy (THz-FDS) combined with multivariate analysis to quantify drug content and tablet density was explored. As the quality of the tablets is highly impacted by the powder flow during manufacturing processes, it is beneficial to build quality assurance before the tableting process. In the last study, the capability of a terahertz frequency-modulated continuous wave (FMCW) radar was for the first time explored to characterise the powder flow dynamics in manufacturing processes. The velocity and density variations of falling powder streams in a vertical tube were non-invasively measured, using a 340-GHz radar instrument with a deep penetration depth through the powder flow and a sample volume resolution in the order of a few cubic centimeters.

In conclusion, it was demonstrated that the THz-FD technique and terahertz FMCW radar are highly promising as non-invasive process analytical tools for real-time quality monitoring of pharmaceutical powders and tablets.

frequency domain spectroscopy

terahertz sensing

multivariate analysis

Pharmaceutical

radar

porosity

powders

API content

tablets

powder flow characterization

tablet density

Kollektorn, MC2-building, Kemivägen 9
Opponent: Dr Daniel Markl, University of Strathclyde, Glasgow, UK.

Författare

Anis Moradikouchi

Chalmers, Mikroteknologi och nanovetenskap, Terahertz- och millimetervågsteknik

Terahertz Frequency-Domain Sensing Combined with Quantitative Multivariate Analysis for Pharmaceutical Tablet Inspection

International Journal of Pharmaceutics,;Vol. 632(2023)

Artikel i vetenskaplig tidskrift

Terahertz Frequency Domain Sensing for Fast Porosity Measurement of Pharmaceutical Tablets

International Journal of Pharmaceutics,;Vol. 618(2022)

Artikel i vetenskaplig tidskrift

Non-Destructive Characterization Of Pharmaceutical Tablets Using Terahertz Frequency Domain Spectroscopy

International Conference on Infrared, Millimeter, and Terahertz Waves, IRMMW-THz,;Vol. 2019-September(2019)

Paper i proceeding

Terahertz radar diagnostics of powder dynamics in pharmaceutical manufacturing, Anis Moradikouchi, Marlene Bonmann, Tomas Bryllert, Anders Sparén, Staffan Folestad, Jonas Johansson, Jan Stake, Helena Rodilla

pharmaceutical tablets are manufactured through the compaction of powder blends or granules in batch or continuous processes. In continuous manufacturing, real-time assurance of quality becomes essential to ensure that the final product meets the quality standards approved by manufacturers and regulatory authorities. Process analytical methods used for real-time monitoring and control should be rapid, non-destructive, and suitable to be conducted in the manufacturing area. This thesis demonstrates the terahertz frequency domain technique, based on all-electronic solutions, as a fast non-destructive sensing technique, with the advantage of a deep penetration depth, high dynamic range, and miniaturization capabilities for real-time monitoring of the key physical properties such as tablet density and porosity. In addition, taking advantage of the lower scattering effect of the THz region compared to higher frequencies, the feasibility of terahertz frequency domain spectroscopy combined with multivariate analysis to quantify drug content and tablet density was explored. As the quality of the tablets is highly impacted by the powder flow during manufacturing processes, it is beneficial to build quality assurance before the tableting process. In the last study, the capability of a terahertz frequency-modulated continuous wave radar was for the first time explored to characterise the powder flow dynamics, which will enable the real-time quality monitoring of powder flow for pharmaceutical operations.

Terahertsteknik för tillverkning av moderna läkemedel

Stiftelsen för Strategisk forskning (SSF) (ID17-0011), 2017-12-01 -- 2023-12-31.

Styrkeområden

Informations- och kommunikationsteknik

Hälsa och teknik

Materialvetenskap

Infrastruktur

Kollberglaboratoriet

Ämneskategorier

Elektroteknik och elektronik

ISBN

978-91-7905-828-9

Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 5294

Utgivare

Chalmers

Kollektorn, MC2-building, Kemivägen 9

Opponent: Dr Daniel Markl, University of Strathclyde, Glasgow, UK.

Mer information

Senast uppdaterat

2023-04-14