title: Eudragit E accelerated the diketopiperazine formation of enalapril maleate determined by thermal FTIR microspectroscopic technique.
abstract: OBJECTIVE
  Enalapril may undergo the thermal-induced intramolecular interaction to cause an enalapril diketopiperazine (DKP) formation. It is interesting to study the influence of Eudragit E, as a coating polymer, on the stability of enalapril maleate. The reaction kinetics of the solid-state degradation process of pure enalapril maleate and Eudragit E/enalapril maleate mixture with different weight ratios were examined. The mechanism of solid-state interaction between Eudragit E and enalapril maleate was also discussed.
  
  
  METHODS
  The cast samples of pure enalapril maleate or Eudragit E/enalapril maleate mixture after evaporating the solvent were prepared on an aluminum foil and also determined by reflectance Fourier transform infrared (FTIR) microspectroscopy equipped with thermal analyzer.
  
  
  RESULTS
  The result indicates that the interaction might occur between enalapril maleate and Eudragit E in the solid state after evaporating the solvent. The thermal-dependent FTIR spectra show that not only the formation of DKP but also the six-membered cyclic anhydride occurred in the enalapril maleate/Eudragit E mixture in the heating process. Two pathways for solid-sate interaction were proposed. The stability of enalapril maleate was dependent on the weight ratio of enalapril maleate and Eudragit E. The activation energy (n = 3) of DKP formation for pure enalapril maleate was about 141.2+/-0.7 kJ/mol, but it was reduced significantly to 86.7+/-0.8 kJ/mol after interaction with Eudragit E (weight ratio: 1:1), suggesting Eudragit E might exacerbate the degradation of enalapril maleate. However, the degradation accelerated by Eudragit E was reduced in high content of Eudragit E.
  
  
  CONCLUSIONS
  When the weight ratio of both components was 1:1, Eudragit E might interact with the carboxyl group of maleic acid to exacerbate the degradation of enalapril maleate. However, the excess amount of Eudragit E might somewhat reduce the degradation of enalapril, due to the interaction that occurred between Eudragit E and carboxyl group of enalapril.
authors.affiliation: Department of Applied Chemistry, National ChiaYi University, ChiaYi, Taiwan, Republic of China.
authors.forename: Shun-Li
authors.initials: SL
authors.lastname: Wang
authors.forename: Shan-Yang
authors.initials: SY
authors.lastname: Lin
authors.forename: Ting-Fang
authors.initials: TF
authors.lastname: Chen
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Cheng
mesh_terms: D000465:Algorithms; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism*; D054659:Diketopiperazines; D004656:Enalapril / Q000378:metabolism*; D005079:Excipients / Q000494:pharmacology; D007700:Kinetics; D008298:Maleates / Q000378:metabolism; D008689:Methacrylates / Q000494:pharmacology*; D008768:Methylmethacrylates; D010879:Piperazines / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D054659:Diketopiperazines; D005079:Excipients; D008298:Maleates; D008689:Methacrylates; D008768:Methylmethacrylates; D010879:Piperazines; C102808:Eudragit-E; D004656:Enalapril; C030272:maleic acid