Reaction Kinetics of Solid-state Cyclization of Enalapril Maleate Investigated by Isothermal FT-IR Microscopic System

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概要

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• To investigate the reaction kinetics of the solid-state degradation process of enalapril maleate, a Fourier transform infrared microspectroscope equipped with thermal analyzer(thermal FT-IR microscopic system)was used. The isothermal stability study was conducted at 120-130℃ for 1-2h and changes in the three-dimensional plots of the IR spectra of enalapril maleate with respect to heating time were observed. The study indicates that the bands at 1649, 1728, and 1751cm^<-1> assigned to intact enalapril maleate gradually reduced in peak intensity with heating time. However, the peak intensities at 1672 and 1738cm^<-1>(due to enalapril diketopiperazine(DKP)formation)and at 3250cm^<-1>(corresponding to water formation)gradually increased with heating time. The solid-state diketopiperazine formation and the degradation process of enalapril maleate via intramolecular cyclization were found to be simultaneous. The isothermal decomposition curves were sigmoidal and were characterized by induction and acceleration periods, indicating the presence of autocatalytic solid-state decompositions. Moreover, the power-law equation(n=1/4)was found to provide the best fit to the kinetics of decomposition. This isothermal FT-IR microscopic system was easily used to investigate the degradation of enalapril maleate and the concomitant formation of DKP. The solid-state reaction of enalapril maleate required an activation energy of 195±12kJ/mol to undergo the processes of decomposition and intramolecular cyclization.

• 公益社団法人日本薬学会の論文
• 2001-04-01

著者

• Lin S‐y

  Veterans General Hospital‐taipei Taipei Twn

• Chen Ting-fang

  Biopharmaceutics Laboratory Department Of Medical Research And Education Veterans General Hospital-t

• WANG Shun-Li

  Biopharmaceutics Laboratory, Department of Medical Research & Education, Veterans General Hospital-T

• LIN Shan-Yang

  Biopharmaceutics Laboratory, Department of medical Research & Education, Veterans General Hospital-T

• Wang Shun-li

  Biopharmaceutics Laboratory Department Of Medical Research & Education Veterans General Hospital

• Lin Shan-yang

  Biopharmaceutical Laboratory Department Of Medical Reseach And Education Veterans General Hospital-t

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• Reaction Kinetics of Solid-state Cyclization of Enalapril Maleate Investigated by Isothermal FT-IR Microscopic System
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