Global approach for the validation of an in-line Raman spectroscopic method to determine the API content in real-time during a hot-melt extrusion process
Netchacovitch, Lauranne; Thiry, Justine; De Bleye, Charlotteet al.
[en] Since the Food and Drug Administration (FDA) published a guidance based on the Process Analytical Technology (PAT) approach, real-time analyses during manufacturing processes are in real expansion.
In this study, in-line Raman spectroscopic analyses were performed during a Hot-Melt Extrusion (HME) process to determine the Active Pharmaceutical Ingredient (API) content in real-time. The method was validated based on a univariate and a multivariate approach and the analytical performances of the obtained models were compared. Moreover, on one hand, in-line data were correlated with the real API concentration present in the sample quantified by a previously validated off-line confocal Raman microspectroscopic method. On the other hand, in-line data were also treated in function of the concentration based on the weighing of the components in the prepared mixture. The importance of developing quantitative methods based on the use of a reference method was thus highlighted. The method was validated according to the total error approach fixing the acceptance limits at ± 15% and the α risk at ± 5%. This method reaches the requirements of the European Pharmacopeia norms for the uniformity of content of single-dose preparations. The validation proves that future results will be in the acceptance limits with a previously defined probability.
Finally, the in-line validated method was compared with the off-line one to demonstrate its ability to be used in routine analyses.
Research center :
Centre Interfacultaire de Recherche du Médicament - CIRM
Thiry, Justine ; Université de Liège > Département de pharmacie > Pharmacie galénique
De Bleye, Charlotte ; Université de Liège > Département de pharmacie > Département de pharmacie
Dumont, Elodie ; Université de Liège > Département de pharmacie > Chimie analytique
Cailletaud, Johan ; Université de Liège > Département de pharmacie > Chimie analytique
Sacre, Pierre-Yves ; Université de Liège > Département de pharmacie > Chimie analytique
Evrard, Brigitte ; Université de Liège > Département de pharmacie > Pharmacie galénique
Hubert, Philippe ; Université de Liège > Département de pharmacie > Chimie analytique
Ziemons, Eric ; Université de Liège > Département de pharmacie > Département de pharmacie
Language :
English
Title :
Global approach for the validation of an in-line Raman spectroscopic method to determine the API content in real-time during a hot-melt extrusion process
[1] Netchacovitch, L., Thiry, J., De Bleye, C., Chavez, P.-F., Krier, F., Sacré, P.-Y., Evrard, B., Hubert, Ph., Ziemons, E., Vibrational spectroscopy and microspectroscopy analyzing qualitatively and quantitatively pharmaceutical hot melt extrudates. J. Pharm. Biomed. Anal. 113 (2015), 21–33.
[2] U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Guidance for Industry: PAT – A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance, 2004.
[3] Hinz, D.C., Process analytical technologies in the pharmaceutical industry: the FDA's PAT initiative. Anal. Bioanal. Chem. 384 (2006), 1036–1042.
[4] Chalus, P., Roggo, Y., Ulmschneider, M., La spectroscopie Raman: un outil pour répondre à l'initiative “process analytical technology” (PAT) dans l'industrie pharmaceutique. Spectra Anal. 252 (2006), 17–22.
[5] Rathore, A.S., Bhambure, R., Ghare, V., Process analytical technology (PAT) for biopharmaceutical products. Anal. Bioanal. Chem. 398 (2010), 137–154.
[6] McCreery, R.L., Raman Spectroscopy for Chemical Analysis. 2000, John Wiley and Sons, Columbus.
[8] Thiry, J., Krier, F., Evrard, B., A review of pharmaceutical extrusion: critical process parameters and scaling-up. Int. J. Pharm. 479 (2015), 227–240.
[9] Monteyne, T., Heeze, L., Oldörp, K., Vervaet, C., Remon, J.-P., De Beer, T., Vibrational spectroscopy to support the link between rheology and continuous twin-screw melt granulation on molecular level: a case study. Eur. J. Pharm. Biopharm. 103 (2016), 127–135.
[10] Van Renterghem, J., Kumar, A., Vervaet, C., Remon, J.-P., Nopens, I., Vander Heyden, Y., De Beer, T., Elucidation and visualization of solid-state transformation and mixing in a pharmaceutical mini hot melt extrusion process using in-line Raman spectroscopy. Int. J. Pharm. 517 (2017), 119–127.
[11] Saerens, L., Dierickx, L., Lenain, B., Vervaet, C., Remon, J.P., Beer, T.D., Raman spectroscopy for the in-line polymer-drug quantification and solid state characterization during a pharmaceutical hot-melt extrusion process. Eur. J. Pharm. Biopharm. 77 (2011), 158–163.
[12] Saerens, L., Vervaet, C., Remon, J.P., De Beer, T., Visualization and process understanding of material behavior in the extrusion barrel during a hot-melt extrusion process using raman spectroscopy. Anal. Chem. 85 (2013), 5420–5429.
[13] Saerens, L., Segher, N., Vervaet, C., Remon, J.P., De Beer, T., Validation of an in-line Raman spectroscopic method for continuous active pharmaceutical ingredient quantification during pharmaceutical hot-melt extrusion. Anal. Chim. Acta 806 (2014), 180–187.
[14] Hubert, Ph., Nguyen-Huu, J.-J., Boulanger, B., Chapuzet, E., Chiap, P., Cohen, N., Compagnon, P.-A., Dewé, W., Feinberg, M., Lallier, M., Laurentie, M., Mercier, N., Muzard, G., Nivet, C., Valat, L., Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal – part I. J. Pharm. Biomed. Anal. 36 (2004), 579–586.
[15] Hubert, Ph., Nguyen-Huu, J.-J., Boulanger, B., Chapuzet, E., Chiap, P., Cohen, N., Compagnon, P.-A., Dewé, W., Feinberg, M., Lallier, M., Laurentie, M., Mercier, N., Muzard, G., Nivet, C., Valat, L., Rozet, E., Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal – part II. J. Pharm. Biomed. Anal. 45 (2007), 70–81.
[16] Hubert, Ph., Nguyen-Huu, J.-J., Boulanger, B., Chapuzet, E., Cohen, N., Compagnon, P.-A., Dewé, W., Feinberg, M., Laurentie, M., Mercier, N., Muzard, G., Valat, L., Rozet, E., Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal – part III. J. Pharm. Biomed. Anal. 45 (2007), 82–96.
[17] Hubert, Ph., Nguyen-Huu, J.-J., Boulanger, B., Chapuzet, E., Cohen, N., Compagnon, P.-A., Dewé, W., Feinberg, M., Laurentie, M., Mercier, N., Muzard, G., Valat, L., Rozet, E., Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal – part IV. J. Pharm. Biomed. Anal. 48 (2008), 760–771.
[18] International Conference on Harmonization (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use, Topic Q2 (R1), Validation of Analytical Procedures: Text and Methodology, Geneva, 2005.
[19] Netchacovitch, L., Thiry, J., De Bleye, C., Dumont, E., Dispas, A., Hubert, C., Krier, F., Sacré, P.-Y., Evrard, B., Hubert, Ph, Ziemons, E., A simple calibration approach based on film-casting for confocal Raman microscopy to support the development of a hot-melt extrusion process. Talanta 154 (2016), 392–399.
[20] Itraconazole, Monograph 01/2011:1335, European Pharmacopeia 7.0.