Detection of trace crystallinity in an amorphous system using Raman microscopy and chemometric analysis

• Published in: European journal of pharmaceutical sciences Vol. 42; no. 1; pp. 45 - 54
• Main Authors: Widjaja, Effendi, Kanaujia, Parijat, Lau, Grace, Ng, Wai Kiong, Garland, Marc, Saal, Christoph, Hanefeld, Andrea, Fischbach, Matthias, Maio, Mario, Tan, Reginald B.H.
• Format: Journal Article
• Language: English
• Published: Kindlington Elsevier B.V 18.01.2011; Elsevier
• Subjects: Active pharmaceutical ingredients; Algorithms; Amorphous; Band-target entropy minimization; Biological and medical sciences; Crystallization; Drug Compounding; Drug Stability; Drug Storage; Entropy; Fenofibrate - chemistry; Formulation; General pharmacology; Hot melt extrusion; Medical sciences; Microscopy - methods; Microscopy, Electron, Scanning; Pharmaceutical Preparations - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phase Transition; Polymorphism; Raman microscopy; Spectrum Analysis, Raman - methods; Surface Properties; Target transformation factor analysis; Trace crystallinity; X-Ray Diffraction; Trace crystallinity; Target transformation factor analysis; Amorphous; Band-target entropy minimization; Raman microscopy; Formulation; Hot melt extrusion; Active pharmaceutical ingredients; Polymorphism; Hot melt; Pharmaceutical technology; Targeting; Entropy; Crystallinity; Target; Microscopy; Extrusion; Active ingredient; Detection; Chemometrics
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2010.10.004

A novel analytical method to detect and characterize active pharmaceutical ingredient (API) trace crystallinity in an amorphous system using Raman microscopy and chemometric methods, namely band-target entropy minimization (BTEM) and target transformation factor analysis (TTFA) is developed. The method starts with Raman mapping measurements performed on some random areas of the amorphous system. This is followed by chemometric data analysis. In the case of a system without any a priori information, the BTEM algorithm is used to recover a set of pure component Raman spectral estimates followed by component and/or crystal structure identification. In the case of a system with some a priori information, TTFA is used to predict the presence or existence of a suspected component and/or crystal structure in the observed system. Four different amorphous systems were used as models. It is demonstrated that combined Raman microscopy and chemometric methods (BTEM or TTFA) outperformed powder X-ray diffraction (PXRD) in detecting trace crystallinity in amorphous systems. The spatial distributions of drug and polymer can also be directly obtained in order to study the homogeneity of the APIs in the solid dispersions. The present methodology appears very general and applicable to many other types of systems.