title: Thermal-Dependent dehydration process and intramolecular cyclization of lisinopril dihydrate in the solid state.
abstract: 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.
authors.affiliation: Department of Medical Research & Education, Veterans General Hospital-Taipei, Shih-Pai, Republic of China.
authors.forename: S L
authors.initials: SL
authors.lastname: Wang
authors.forename: S Y
authors.initials: SY
authors.lastname: Lin
authors.forename: T F
authors.initials: TF
authors.lastname: Chen
mesh_terms: 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
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D054659:Diketopiperazines; D010879:Piperazines; D014867:Water; D017706:Lisinopril