Drug content determination of low-dosed hot-melt extruded filaments using Raman spectroscopy

Abstract

The aim of this study was to evaluate the suitability of a non-disruptive Raman spectroscopic method to quantify drug concentrations below 5 w% within a polymer matrix produced by hot-melt extrusion (HME). For calibration, praziquantel (PZQ)—polyvinylpyrrolidone-vinylacetat-copolymer (PVP-VA) mixtures were extruded. By focusing the laser light of the Raman probe to a diameter of 1 mm and implementing a self-constructed filament holder, the signal-to-noise (S/N) ratio could be reduced considerably. The obtained Raman spectra show quite high fluorescence, which is likely to be caused by dissolved pharmaceutical active ingredient (API) in the polymer matrix. For content determination, HPLC analysis was conducted as a reference method using the same filament segments. A partial least squares (PLS) model, regressing the PZQ concentrations from HPLC method analysis versus the off-line collected Raman spectra, was developed. The linear correlation for a suitable extrusion run for the production of low-dosed filaments (extrusion 1, two kneading zones) is acceptable (R² = 0.9915) while the correlation for a extrusion set-up with low miscibility (extrusion 2; without kneading zone) is unacceptable (R² = 0.5349). The predictive performance of the calibration model from extrusion 1 is rated by the root mean square error of estimation (RMSEE), which was 0.08%. This calibration can now be used to validate the content of low-dosed filaments during HME.

Keywords:

• Hot-melt extrusion
• low-dosed
• Raman spectroscopy
• drug content determination
• non-destructive measurement
• in-line analytics

Acknowledgements

The team responsible for the work presented here would like to acknowledge Peter Kleinebudde for his scientific input and support for continuous in-line Raman measurements.

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

The data that support the findings of this study are available from the corresponding authors, [RC, BF], upon reasonable request.

Additional information

Funding

This research was funded by Bundesministerium für Bildung und Forschung–Project ‘ProMat Leben–Polymere’‘PolyPrint’, project number.: 13XP5064B.