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Updated: Jun 8, 2026
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A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
Raman spectroscopy for the in-line polymer-drug quantification and solid state characterization during a
L Saerens1, L Dierickx, B Lenain
1Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium. Lien.Saerens@UGent.be
Summary
Raman spectroscopy effectively monitors active pharmaceutical ingredient (API) concentration and drug solid state during hot-melt extrusion. This Process Analytical Technology (PAT) tool enables real-time analysis for pharmaceutical manufacturing.
Area of Science:
- Pharmaceutical Technology
- Analytical Chemistry
- Spectroscopy
Background:
- Hot-melt extrusion (HME) is a key pharmaceutical process for drug formulation.
- Process Analytical Technology (PAT) aims to enhance process understanding and control.
- Raman spectroscopy offers non-invasive, in-line analytical capabilities.
Purpose of the Study:
- To assess Raman spectroscopy as a PAT tool for real-time monitoring of API concentration during HME.
- To evaluate its suitability for characterizing polymer-drug solid states in HME products.
- To correlate spectroscopic data with drug physical form and interactions.
Main Methods:
- In-line Raman spectroscopy was employed during the hot-melt extrusion of metoprolol tartrate (MPT) and Eudragit polymers.
- Partial Least Squares (PLS) modeling was used for quantitative API concentration determination.
- Solid-state characterization involved analyzing spectral changes related to amorphous content and polymer-drug interactions.
- Differential Scanning Calorimetry (DSC) was used for validation.
Main Results:
- A validated PLS model achieved accurate real-time MPT concentration prediction (R²=0.997, RMSEP=0.59%).
- Raman spectra indicated amorphous MPT in solid solutions and distinct peak shifts in solid dispersions/solutions, suggesting polymer-drug interactions (likely hydrogen bonds).
- DSC analysis corroborated the Raman spectroscopic findings on solid state and interactions.
Conclusions:
- Raman spectroscopy is a viable PAT tool for in-line API quantification during pharmaceutical HME.
- It can effectively monitor polymer-drug solid state transformations and interactions in real-time.
- This technology holds potential for improving process control and product quality in HME manufacturing.
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