Detection of trace crystallinity in an amorphous system using Raman microscopy and chemometric analysis.
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.
Institute of Chemical and Engineering Sciences, 1 Pesek Road, Jurong Island, Singapore, Singapore. effendi_widjaja@ices.a-star.edu.sg
Effendi
E
Widjaja
Parijat
P
Kanaujia
Grace
G
Lau
Wai Kiong
WK
Ng
Marc
M
Garland
Christoph
C
Saal
Andrea
A
Hanefeld
Matthias
M
Fischbach
Mario
M
Maio
Reginald B H
RB
Tan
D000465:Algorithms; D003460:Crystallization; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D019277:Entropy; D011345:Fenofibrate / Q000737:chemistry; D008853:Microscopy / Q000379:methods*; D008855:Microscopy, Electron, Scanning; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D044367:Phase Transition; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013499:Surface Properties; D014961:X-Ray Diffraction
D004364:Pharmaceutical Preparations; D011345:Fenofibrate