Terahertz Frequency-Domain Sensing Combined with Quantitative Multivariate Analysis for Pharmaceutical Tablet Inspection
Journal article, 2023

Near infrared (NIR) and Raman spectroscopy combined with multivariate analysis are established techniques for the identification and quantification of chemical properties of pharmaceutical tablets like the concentration of active pharmaceutical ingredients (API). However, these techniques suffer from a high sensitivity to particle size variations and are not ideal for the characterization of physical properties of tablets such as tablet density. In this work, we have explored the feasibility of terahertz frequency-domain spectroscopy, with the advantage of low scattering effects, combined with multivariate analysis to quantify API concentration and tablet density. We studied 33 tablets, consisting of Ibuprofen, Mannitol, and a lubricant with API concentration and filler particle size as the design factors. The terahertz signal was measured in transmission mode across the frequency range 750 GHz to 1.5 THz using a vector network analyzer, frequency extenders, horn antennas, and four off-axis parabolic mirrors. The attenuation spectral data were pre-processed and orthogonal partial least square (OPLS) regression was applied to the spectral data to obtain quantitative prediction models for API concentration and tablet density. The performance of the models was assessed using test sets. While a fair model was obtained for API concentration, a high-quality model was demonstrated for tablet density. The coefficient of determination (𝑅2) for the calibration set was 0.97 for tablet density and 0.98 for API concentration, while the relative prediction errors for the test set were 0.7% and 6% for tablet density and API concentration models, respectively. In conclusion, terahertz spectroscopy demonstrated to be a complementary technique to Raman and NIR spectroscopy, which enables the characterization of physical properties of tablets like tablet density, and the characterization of API concentration with the advantage of low scattering effects.

Multivariate analysis

Frequency domain

Pharmaceutical tablets

Tablet density

Terahertz spectroscopy

API concentration

Non-destructive

Author

Anis Moradikouchi

Chalmers, Microtechnology and Nanoscience (MC2), Terahertz and Millimetre Wave Laboratory

Anders Sparén

AstraZeneca R&D

Olof Svensson

AstraZeneca R&D

Staffan Folestad

AstraZeneca AB

Jan Stake

Chalmers, Microtechnology and Nanoscience (MC2), Terahertz and Millimetre Wave Laboratory

Helena Rodilla

Chalmers, Microtechnology and Nanoscience (MC2), Terahertz and Millimetre Wave Laboratory

International Journal of Pharmaceutics

0378-5173 (ISSN) 1873-3476 (eISSN)

Vol. 632 122545

THz sensors aiding smart production of precision medicines

Swedish Foundation for Strategic Research (SSF) (ID17-0011), 2017-12-01 -- 2023-12-31.

Areas of Advance

Information and Communication Technology

Health Engineering

Materials Science

Infrastructure

Kollberg Laboratory

Subject Categories

Electrical Engineering, Electronic Engineering, Information Engineering

Probability Theory and Statistics

DOI

10.1016/j.ijpharm.2022.122545

PubMed

36581106

More information

Latest update

1/11/2024