Eudragit E accelerated the diketopiperazine formation of enalapril maleate determined by thermal FTIR microspectroscopic technique.
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.
Wang
Shun-Li
SL
Department of Applied Chemistry, National ChiaYi University, ChiaYi, Taiwan, Republic of China.
Lin
Shan-Yang
SY
Chen
Ting-Fang
TF
Cheng
Wen-Ting
WT
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
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