title: Multivariate data analysis as a tool to investigate the reaction kinetics of intramolecular cyclization of enalapril maleate studied by isothermal and non-isothermal FT-IR microscopy.
abstract: In this paper, the use of multivariate data analysis approach to investigate the kinetics of solid-state reaction monitored via FT-IR thermal microscopy is discussed. The solid-state degradation of enalapril maleate was monitored non-isothermally at temperature range from 25 to 200 degrees C and isothermally at various temperatures (115, 120, 125, 130, and 135 degrees C) for a few hours. The collected FT-IR spectra were subjected to self-modeling curve resolution (SMCR) in order to elucidate the pure component spectral estimates. Subsequently, the relative contributions from the observed species could be obtained by projecting the pure component spectral estimates onto the collected FT-IR spectra. Accordingly, the conversion factors from enalapril maleate to diketopiperazine were calculated and were fitted to various solid-state reaction models. The activation energy values (E(a)) calculated from seven nucleation models were ranging from 176.4 to 193.9 kJ/mol. This multivariate data analysis approach proves to be an effective tool for analyzing the kinetic spectroscopic data having a high degree of overlap between original compound and its degradation product since the information from the whole spectral range is used.
authors.affiliation: Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research (A*STAR), 1 Pesek Road, Jurong Island, Singapore 627833, Singapore. effendi_widjaja@ices.a-star.edu.sg
authors.forename: Effendi
authors.initials: E
authors.lastname: Widjaja
authors.forename: Geok Hong
authors.initials: GH
authors.lastname: Lim
authors.forename: Pui Shan
authors.initials: PS
authors.lastname: Chow
authors.forename: Selvi
authors.initials: S
authors.lastname: Tan
mesh_terms: D003500:Cyclization; D054659:Diketopiperazines / Q000138:chemical synthesis; D004355:Drug Stability; D004656:Enalapril / Q000737:chemistry*; D007700:Kinetics; D015999:Multivariate Analysis; D012680:Sensitivity and Specificity; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013696:Temperature
chemical_list: D054659:Diketopiperazines; D004656:Enalapril