Abstract
Purpose
Although the characterization of the chemical and spatial distribution of compounds within a pharmaceutical tablet is still not a routine task, applying Raman spectroscopy with data analysis methods gives the possibility to obtain in-depth information on tablet quality rapidly. However, constraints such as analysis time, laser intensity, and spot size influence the quality of acquired spectra resulting in low signal-to-noise ratio spectra. Therefore, this study proposes a method to characterize a solid heterogeneous pharmaceutical product (e.g., a tablet) based on the product’s Raman chemical map.
Methods
In this work, surface Raman data were acquired using a simple and rapid method. An algorithm based on the hierarchical application of multivariate curve resolution with log-likelihood maximization combined with principal component analysis was used to blind identify the compounds and create a chemical map.
Results
Although the direct application of multivariate curve resolution algorithms did not allow a complete tablet characterization, the hierarchical application enabled individual compounds acquired from the mixed spectra to be identified and their chemical distribution in the tablet to be mapped without the use of external references. Results were successfully benchmarked against the EDXS analysis.
Conclusions
Innovations in multivariate methods could help overcome challenges and constraints in data acquisition. This method was, for example, found to be more robust against the presence of spectral outliers. It is promising for 3D analysis of real and complex samples.
Graphical abstract
Similar content being viewed by others
References
European Commission. Chapter 5. EU Guidel Good Manuf Pract Med Prod Hum Vet Use Part 1. 2014.
Moriyama K. Advanced applications of Raman imaging for deeper understanding and better quality control of formulations. Curr Pharm Des. 2016;22:4912–6.
Schmitt PD. Recent advances in nonlinear optical analyses of pharmaceutical materials in the solid state. Mol Pharm. 2017;14:555–65.
Démuth B, Farkas A, Pataki H, Balogh A, Szabó B, Borbás E, et al. Detailed stability investigation of amorphous solid dispersions prepared by single-needle and high speed electrospinning. Int J Pharm. 2016;498:234–44.
Aleksovski A, Van Bockstal P-J, Roškar R, Sovány T, Regdon G, De Beer T, et al. Comparison of metoprolol tartrate multiple-unit lipid matrix systems produced by different technologies. Eur J Pharm Sci. 2016;88:233–45.
Katewongsa P, Terada K, Phaechamud T. Spatial distributing lubricants from Raman mapping and scanning electron microscopy–energy dispersive X-ray spectroscopy on cetirizine dihydrochloride fast disintegrating tablet properties. J Pharm Investig. 2017;47:249–62.
Scoutaris N, Vithani K, Slipper I, Chowdhry B, Douroumis D. SEM/EDX and confocal Raman microscopy as complementary tools for the characterization of pharmaceutical tablets. Int J Pharm. 2014;470:88–98.
Coic L, Sacre P-Y, Avohou H, Deidda R, De Bleye C, Dumont E, et al. Recent developments of Raman spectroscopy for the qualitative analysis of falsified and substandard medicines. Eur Pharm Rev. 2018;23:6–8.
Smith R, Wright KL, Ashton L. Raman spectroscopy: an evolving technique for live cell studies. Analyst. 2016;141:3590–600.
De Beer T, Burggraeve A, Fonteyne M, Saerens L, Remon JP, Vervaet C. Near infrared and Raman spectroscopy for the in-process monitoring of pharmaceutical production processes. Int J Pharm. 2011;417:32–47.
Assi S. Raw material identification using dual laser handheld Raman spectroscopy. Eur Pharm Rev. 2013;18:23–31.
Hossain A, Nandi U, Fule R, Nokhodchi A, Maniruzzaman M. Advanced surface chemical analysis of continuously manufactured drug loaded composite pellets. J Colloid Interface Sci. 2017;492:157–66.
Edinger M, Bar-Shalom D, Rantanen J, Genina N. Visualization and non-destructive quantification of inkjet-printed pharmaceuticals on different substrates using Raman spectroscopy and Raman chemical imaging. Pharm Res. 2017;34:1023–36.
Cebeci-Maltas. Raman imaging for the evaluation of counterfeit vs guenine Cialis(R) tablets.
Ying Y, Łuczak A, Iqbal Z. Use of Raman in analysing polymorphism in pharmaceutical drugs. Eur Pharm Rev. 2016;21:26–30.
Scoutaris N. Raman: a valuable tool in high-throughput screening. Eur Pharm Rev. 2016;21:22–5.
Feltham VLC. Raman spectroscopy of pharmaceutical ingredients in a humidity-controlled atmosphere. 2015 [cited 2017 Sep 15]; Available from: http://www.spectroscopyonline.com/raman-spectroscopy-pharmaceutical-ingredients-humidity-controlled-atmosphere
Hisada H, Inoue M, Koide T, Carriere J, Heyler R, Fukami T. Direct high-resolution imaging of crystalline components in pharmaceutical dosage forms using low-frequency Raman spectroscopy. Org Process Res Dev. 2015;19:1796–8.
Nie H, Liu Z, Marks BC, Taylor LS, Byrn SR, Marsac PJ. Analytical approaches to investigate salt disproportionation in tablet matrices by Raman spectroscopy and Raman mapping. J Pharm Biomed Anal. 2016;118:328–37.
Li X, Chen H, Zhu Q, Liu Y, Lu F. Analysis of low active-pharmaceutical-ingredient signal drugs based on thin layer chromatography and surface-enhanced Raman spectroscopy. J Pharm Biomed Anal. 2016;131:410–9.
Farkas A, Nagy B, Démuth B, Balogh A, Pataki H, Nagy ZK, et al. Variable clustering and spectral angle mapper-orthogonal projection method for Raman mapping of compound detection in tablets: Variable clustering for Raman mapping of compound detection in tablet. J Chemom. 2017;31: e2861.
Farkas A, Vajna B, Sóti PL, Nagy ZK, Pataki H, Van der Gucht F, et al. Comparison of multivariate linear regression methods in micro-Raman spectrometric quantitative characterization: Multivariate linear regression methods. J Raman Spectrosc. 2015;46:566–76.
Cebeci Maltaş D, Kwok K, Wang P, Taylor LS, Ben-Amotz D. Rapid classification of pharmaceutical ingredients with Raman spectroscopy using compressive detection strategy with PLS-DA multivariate filters. J Pharm Biomed Anal. 2013;80:63–8.
Davis BM, Hemphill AJ, Cebeci Maltaş D, Zipper MA, Wang P, Ben-Amotz D. Multivariate hyperspectral raman imaging using compressive detection. Anal Chem. 2011;83:5086–92.
Boiret M, Gorretta N, Ginot Y-M, Roger J-M. An iterative approach for compound detection in an unknown pharmaceutical drug product: application on Raman microscopy. J Pharm Biomed Anal. 2016;120:342–51.
Nagy B, Farkas A, Balogh A, Pataki H, Vajna B, Nagy ZK, et al. Quantification and handling of nonlinearity in Raman micro-spectrometry of pharmaceuticals. J Pharm Biomed Anal. 2016;128:236–46.
Fauteux-Lefebvre C, Lavoie F, Gosselin R. A hierarchical multivariate curve resolution methodology to identify and map compounds in spectral images. Anal Chem. 2018;90:13118–25.
Hudon S, Lapointe-Garant P-P, Simard J-S, Pichieri A, Hammond S, Sienkiewicz G, et al. Evaluation of a dry coating technology as a substitute for roller compaction for dry agglomeration applications in the pharmaceutical industry. J Pharm Innov. 2019;14:286–303.
De Juan A, Jaumot J, Tauler R. Multivariate curve resolution (MCR). Solving the mixture analysis problem. Anal Methods. 2014;6:4964–76.
Lavoie FB, Braidy N, Gosselin R. Including noise characteristics in MCR to improve mapping and component extraction from spectral images. Chemom Intell Lab Syst. 2016;153:40–50.
MacQueen J. Some methods for classification and analysis of multivariate observations. Proc Fifth Berkeley Symp Math Stat Probab. 1967;1:281–97.
Funding
This work was supported by the Mitacs Elevate program (IT06238) and the FRQNT Industrial Innovation Scholarship (196489) as well as a matching contribution from Pfizer Canada.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Fauteux-Lefebvre, C., Lavoie, F.B., Hudon, S. et al. Hierarchical Multivariate Curve Resolution Coupled to Raman Imaging for Fast Characterization of Pharmaceutical Tablets. J Pharm Innov 18, 461–471 (2023). https://doi.org/10.1007/s12247-022-09652-y
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12247-022-09652-y