Intramolecular cyclization of diketopiperazine formation in solid-state enalapril maleate studied by thermal FT-IR microscopic system.
The pathway of diketopiperazine (DKP) formation of solid-state enalapril maleate has been studied by using a novel Fourier transform infrared microspectroscope equipped with a thermal analyzer (thermal FT-IR microscopic system). The thermogram of the conventional differential scanning calorimetry (DSC) method was also compared. The results show new evidence of IR peaks at 3250 cm(-1) (the broad O-H stretching mode of water), and at 1738 and 1672 cm(-1) (the carbonyl band of DKP), indicating DKP formation in enalapril maleate via intramolecular cyclization. Moreover, the disappearance of IR peaks from enalapril maleate at 3215 cm(-1) (the secondary amine), 1728 cm(-1) (the carbonyl group of carboxylic acid), and 1649 cm(-1) (the carbonyl stretching of tertiary amide) also confirmed the DKP formation. The thermal FT-IR microscopic system clearly evidenced that the DKP formation in enalapril maleate started from 129 degrees C, and reached a maximum at 137 degrees C. This result was also confirmed by the conventional DSC thermogram of the compressed mixture of KBr powder and enalapril maleate, in which an endothermic peak at 144 degrees C with an extrapolated onset temperature at 137 degrees C was observed. This strongly suggests that the thermal FT-IR microscopic system was able to qualitatively detect the formation of DKP derivatives in solid-state enalapril maleate via intramolecular cyclization.
Lin
Shan-Yang
SY
Department of Medical Research & Education, Veterans General Hospital-Taipei, Taipei, Taiwan, ROC. sylin@vghtpe.gov.tw
Wang
Shun-Li
SL
Chen
Ting-Fang
TF
Hu
Ting-Chou
TC
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003500:Cyclization; D054659:Diketopiperazines; D004656:Enalapril / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
D000806:Angiotensin-Converting Enzyme Inhibitors; D054659:Diketopiperazines; D010879:Piperazines; D004656:Enalapril