Thermal-Dependent dehydration process and intramolecular cyclization of lisinopril dihydrate in the solid state.
The pathway of dehydration and intramolecular cyclization of lisinopril dihydrate in the solid state was investigated using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and a combination of thermal analyzer with Fourier transform infrared microspectroscopy (thermal FT-IR microscopic system). The results indicate that the dehydration from the solid-state lisinopril dihydrate had a two-step process from dihydrate to monohydrate at 76 degrees C and then from monohydrate to anhydrate at 99-101 approximately C, which could be clearly observed from the above three methods. Only the thermal FT-IR microscopic system could give vital information on diketopiperazine (DKP) formation via intramolecular cyclization in anhydrous lisinopril. A new peak at 1670 cm(-1) assigned to the carbonyl band of DKP formation was clearly evidenced. The water of reaction byproduct was liberated at a temperature >157 degrees C and appeared on the IR spectra near 3200-3400 cm(-1). Moreover, the peak at 1574 cm(-1) assigned to carboxylate shifted to 1552 cm(-1) due to the DKP formation. The peak at 1670 cm(-1) related to the DKP formation changed slightly in intensity from 147 degrees C and significantly near 157 degrees C. DSC and TGA methods were poor for use in supplying information on DKP formation in lisinopril. The thermal FT-IR microscopic system is useful from the view point that it can quickly and directly show the solid-state stability of drug.
Wang
S L
SL
Department of Medical Research & Education, Veterans General Hospital-Taipei, Shih-Pai, Republic of China.
Lin
S Y
SY
Chen
T F
TF
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D003500:Cyclization; D054659:Diketopiperazines; D017706:Lisinopril / Q000737:chemistry*; D010879:Piperazines / Q000737:chemistry; D011786:Quality Control; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D014867:Water / Q000737:chemistry
D000806:Angiotensin-Converting Enzyme Inhibitors; D054659:Diketopiperazines; D010879:Piperazines; D014867:Water; D017706:Lisinopril