In-line NIR spectroscopy for the understanding of polymer-drug interaction during pharmaceutical hot-melt extrusion

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• 作者：Lien Saerens^a ; ^{Lien.Saerens@UGent.be} ; Lien Dierickx^b ; Thomas Quinten^b ; Peter Adriaensens^c ; Robert Carleer^c ; Chris Vervaet^b ; Jean Paul Remon^b ; Thomas De Beer^a
• 关键词：NIR spectroscopy ; Hot-melt extrusion (HME) ; Process Analytical Technology (PAT) ; In-line monitoring ; Continuous production
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2012
• 期刊代码：16_09396411
• 类别：pha
• 出版时间：May, 2012
• 卷：81
• 期：1
• 页码：230-237
• 文件大小：1112 K

摘要

The aim was to evaluate near-infrared spectroscopy for the in-line determination of the drug concentration, the polymer-drug solid-state behaviour and molecular interactions during hot-melt extrusion.

Kollidon庐 SR was extruded with varying metoprolol tartrate (MPT) concentrations (20%, 30%and 40%) and monitored using NIR spectroscopy. A PLS model allowed drug concentration determination. The correlation between predicted and real MPT concentrations was good (R² = 0.97). The predictive performance of the model was evaluated by the root mean square error of prediction, which was 1.54%. Kollidon庐 SR with 40%MPT was extruded at 105 掳C and 135 掳C to evaluate NIR spectroscopy for in-line polymer-drug solid-state characterisation.

NIR spectra indicated the presence of amorphous MPT and hydrogen bonds between drug and polymer in the extrudates. More amorphous MPT and interactions could be found in the extrudates produced at 135 掳C than at 105 掳C. Raman spectroscopy, DSC and ATR FT-IR were used to confirm the NIR observations. Due to the instability of the formulation, only in-line Raman spectroscopy was an adequate confirmation tool. NIR spectroscopy is a potential PAT-tool for the in-line determination of API concentration and for the polymer-drug solid-state behaviour monitoring during pharmaceutical hot-melt extrusion.