The Development of an Inline Raman Spectroscopic Analysis Method as a Quality Control Tool for Hot Melt Extruded Ramipril Fixed-dose Combination Products

Publication date: Available online 11 May 2019Source: International Journal of PharmaceuticsAuthor(s): G.P. Andrews, D.S. Jones, Z. Senta-Loys, A. Almajaan, S. Li, O. Chevallier, C. Elliot, A.M. Healy, J.F. Kelleher, A.M. Madi, G.C. Gilvary, Y. TianAbstractCurrently in the pharmaceutical industry, continuous manufacturing is an area of significant interest. In particular, hot-melt extrusion (HME) offers many advantages and has been shown to significantly reduce the number of processing steps relative to a conventional product manufacturing line. To control product quality during HME without process interruption, integration of inline analytical technology is critical. Vibrational spectroscopy (Raman, NIR and FT-IR) is often employed and used for real-time measurements because of the non-destructive and rapid nature of these analytical techniques. However, the establishment of reliable Process Analytical Technology (PAT) tools for HME of thermolabile drugs is challenging. Indeed, the Raman effect is inherently weak and might be subject to interference. Moreover, during HME, heating and photodecomposition can occur and disrupt spectra acquisition. The aim of this research article was to explore the use of inline Raman spectroscopy to characterise a thermolabile drug, ramipril (RMP), during continuous HME processing. Offline measurements by HPLC, LC-MS and Raman spectroscopy were used to characterise RMP and its main degradation product, ramipril-diketopiperazine (RMP-DKP, impur...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research