Evaluation of distributional homogeneity of pharmaceutical formulation using laser direct infrared imaging

Laser direct infrared imaging; Raman imaging; Homogeneity; Vibrational spectroscopy; Distributional Homogeneity Index (DHI); Pharmaceutical formulations development

Abstract :

[en] The distributional homogeneity of chemicals is a key parameter of solid pharmaceutical formulations. Indeed, it may affect the efficacy of the drug and consequently its safety. Chemical imaging offers a unique insight enabling the visualisation of the different constituents of a pharmaceutical tablet. It allows identifying ingredients poorly distributed offering the possibility to optimize the process parameters or to adapt characteristics of incoming raw materials to increase the final product quality. Among the available chemical imaging tools, Raman imaging is one of the most widely used since it offers a high spatial resolution with well-resolved peaks resulting in a high spectral specificity. However, Raman imaging suffers from sample autofluorescence and long acquisition times. Recently commercialised, laser direct infrared reflectance imaging (LDIR) is a quantum cascade laser (QCL) based imaging technique that offers the opportunity to rapidly analyse samples. In this study, a typical pharmaceutical formulation blend composed of two active pharmaceutical ingredients and three excipients was aliquoted at different mixing time points. The collected aliquots were tableted and analysed using both Raman and LDIR imaging. The distributional homogeneity indexes of one active ingredient image were then computed and compared. The results show that both techniques provided similar conclusions. However, the analysis times were drastically different. While Raman imaging required a total analysis time of 4 hours per tablet to obtain the distribution map of acetylsalicylic acid with a step size of 100 µm, it only took 7.5 minutes to achieve the same decision with LDIR for a single compound. The results obtained in the present study show that LDIR is a promising technique for the analysis of pharmaceutical formulations and that it could be a valuable tool when developing new pharmaceutical formulations.

Research Center/Unit :

CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège

Disciplines :

Pharmacy, pharmacology & toxicology

Author, co-author :

Sacre, Pierre-Yves ; Université de Liège - ULiège > Département de pharmacie > Chimie analytique

Alaoui Mansouri, Mohammed ; Université de Liège - ULiège > CIRM

De Bleye, Charlotte ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie

Coic, Laureen ; Université de Liège - ULiège > Département de pharmacie > Chimie analytique

Hubert, Philippe ; Université de Liège - ULiège > Département de pharmacie > Chimie analytique

Ziemons, Eric ; Université de Liège - ULiège > Département de pharmacie > Chimie analytique

Language :

English

Title :

Evaluation of distributional homogeneity of pharmaceutical formulation using laser direct infrared imaging

Publication date :

25 January 2022

Journal title :

International Journal of Pharmaceutics

ISSN :

0378-5173

eISSN :

1873-3476

Publisher :

Elsevier, Netherlands

Volume :

612

Issue :

121373

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

EC - European Commission
F.R.S.-FNRS - Fonds de la Recherche Scientifique
FWO - Fonds Wetenschappelijk Onderzoek Vlaanderen

Available on ORBi :

since 11 December 2021

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Bibliography

Belu, A.M., Davies, M.C., Newton, J.M., Patel, N., TOF-SIMS characterization and imaging of controlled-release drug delivery systems. Anal. Chem. 72 (2000), 5625–5638, 10.1021/ac000450+.
Bhargava, R., Infrared spectroscopic imaging: the next generation. Appl. Spectrosc. 66:10 (2012), 1091–1120, 10.1366/12-06801.
Bøtker, J., Wu, J.X., Rantanen, J., 2020. Hyperspectral imaging as a part of pharmaceutical product design, in: Data Handling in Science and Technology. Elsevier Ltd, pp. 567–581. https://doi.org/10.1016/B978-0-444-63977-6.00022-5.
Carruthers, H., Clark, D., Clarke, F., Faulds, K., Graham, D., Comparison of Raman and near-infrared chemical mapping for the analysis of pharmaceutical tablets. Appl. Spectrosc. 75:2 (2021), 178–188, 10.1177/0003702820952440.
Chavez, P.-F., Lebrun, P., Sacré, P.-Y., De Bleye, C., Netchacovitch, L., Cuypers, S., Mantanus, J., Motte, H., Schubert, M., Evrard, B., Hubert, P., Ziemons, E., Optimization of a pharmaceutical tablet formulation based on a design space approach and using vibrational spectroscopy as PAT tool. Int. J. Pharm. 486:1-2 (2015), 13–20, 10.1016/j.ijpharm.2015.03.025.
Coic, L., Sacré, P.-Y., Dispas, A., Sakira, A.K., Fillet, M., Marini, R.D., Hubert, P., Ziemons, E., Comparison of hyperspectral imaging techniques for the elucidation of falsified medicines composition. Talanta 198 (2019), 457–463, 10.1016/j.talanta.2019.02.032.
da Costa Filho, P.A., Cobuccio, L., Mainali, D., Rault, M., Cavin, C., Rapid analysis of food raw materials adulteration using laser direct infrared spectroscopy and imaging. Food Control, 113, 2020, 107114, 10.1016/j.foodcont.2020.107114.
Earnshaw, C.J., Carolan, V.A., Richards, D.S., Clench, M.R., Direct analysis of pharmaceutical tablet formulations using matrix-assisted laser desorption/ionisation mass spectrometry imaging. Rapid Commun. Mass Spectrom. 24:11 (2010), 1665–1672, 10.1002/rcm.4525.
Eilers, P.H.C., 2003. A Perfect Smoother. Anal. Chem. 75, 3631–3636. https://doi.org/10.1021/ac034173t.
Farkas, A., Nagy, B., Marosi, G., Quantitative evaluation of drug distribution in tablets of various structures via Raman mapping. Period. Polytech. Chem. Eng., 2017, 1–7.
Fringeli, U.P., Encyclopedia of Spectroscopy and Spectrometry, 1999, Elsevier, 94–109, 10.1016/B978-0-12-374413-5.00104-4.
Gowen, A.A., O'Donnell, C.P., Cullen, P.J., Bell, S.E.J., Recent applications of Chemical Imaging to pharmaceutical process monitoring and quality control. Eur. J. Pharm. Biopharm. 69:1 (2008), 10–22, 10.1016/j.ejpb.2007.10.013.
Klukkert, M., Wu, J.X., Rantanen, J., Carstensen, J.M., Rades, T., Leopold, C.S., Multispectral UV imaging for fast and non-destructive quality control of chemical and physical tablet attributes. Eur. J. Pharm. Sci. 90 (2016), 85–95, 10.1016/j.ejps.2015.12.004.
Novakovic, D., Saarinen, J., Rojalin, T., Antikainen, O., Fraser-Miller, S.J., Laaksonen, T., Peltonen, L., Isomäki, A., Strachan, C.J., Multimodal nonlinear optical imaging for sensitive detection of multiple pharmaceutical solid-state forms and surface transformations. Anal. Chem. 89:21 (2017), 11460–11467, 10.1021/acs.analchem.7b02639.
Prats-Montalbán, J.M., Jerez-Rozo, J.I., Romañach, R.J., Ferrer, A., MIA and NIR chemical Imaging for pharmaceutical product characterization. Chemom. Intell. Lab. Syst. 117 (2012), 240–249, 10.1016/j.chemolab.2012.04.002.
Sacré, P.-Y., De Bleye, C., Chavez, P.-F., Netchacovitch, L., Hubert, P., Ziemons, E., Data processing of vibrational chemical imaging for pharmaceutical applications. J. Pharm. Biomed. Anal. 101 (2014), 123–140, 10.1016/j.jpba.2014.04.012.
Sacré, P.-Y., Lebrun, P., Chavez, P.-F., De Bleye, C., Netchacovitch, L., Rozet, E., Klinkenberg, R., Streel, B., Hubert, P., Ziemons, E., A new criterion to assess distributional homogeneity in hyperspectral images of solid pharmaceutical dosage forms. Anal. Chim. Acta 818 (2014), 7–14, 10.1016/j.aca.2014.02.014.
Sacré, P.-Y., Netchacovitch, L., De Bleye, C., Chavez, P.-F., Servais, C., Klinkenberg, R., Streel, B., Hubert, P., Ziemons, E., Thorough characterization of a self-emulsifying drug delivery system with Raman hyperspectral imaging: a case study. Int. J. Pharm. 484:1-2 (2015), 85–94, 10.1016/j.ijpharm.2015.02.052.
Savitzky, A., Golay, M.J.E., Smoothing and differentiation of data by simplified least squares procedures. Anal. Chem. 36:8 (1964), 1627–1639, 10.1021/ac60214a047.
Scircle, A., Cizdziel, J.V., Tisinger, L., Anumol, T., Robey, D., Occurrence of microplastic pollution at oyster reefs and other coastal sites in the Mississippi Sound, USA: impacts of freshwater inflows from flooding. Toxics, 8, 2020, 35, 10.3390/toxics8020035.
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. 470:1-2 (2014), 88–98, 10.1016/j.ijpharm.2014.05.007.
Stewart, S., Priore, R.J., Nelson, M.P., Treado, P.J., 2012. Raman imaging. Annu Rev Anal Chem (Palo Alto Calif) 5, 337–360. https://doi.org/10.1146/annurev-anchem-062011-143152.
Wahl, P.R., Pucher, I., Scheibelhofer, O., Kerschhaggl, M., Sacher, S., Khinast, J.G., Continuous monitoring of API content, API distribution and crushing strength after tableting via near-infrared chemical imaging. Int. J. Pharm. 518:1-2 (2017), 130–137, 10.1016/j.ijpharm.2016.12.003.