Abstract
The physicochemical characteristics of active pharmaceutical ingredients (APIs) are improved by cocrystal formation. This study investigates the co-crystallization of captopril (CAP) with L-proline (PRO) using the liquid-assisted grinding synthesis method. Solid-state behavior is analyzed through differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), Fourier-transform infrared (FTIR), and Scanning electron microscopy (SEM). DSC analysis showed distinct melting temperatures for CAP (105.27°C) and PRO (223.066°C). In the CAP-PRO system, two eutectics were observed: one at x1 = 0.6 characterized by a melting temperature of 104.81°C, while the second corresponds to x1=0.9 and a temperature of 91.44°C. A pure co-crystal was formed at x1 = 0.8 with a melting temperature of 151.74°C. PXRD revealed that CAP-PRO system showed a new diffraction pattern, indicating a distinct cocrystal structure. FTIR spectra displayed differences in wavenumbers, suggesting intermolecular interactions within the co-crystal. SEM analysis showed differences in crystal morphology between the CAP-PRO co-crystal and individual components. Theoretical Study (DFT) HOMO/LUMO and Molecular electrostatic potential (MESP) was also conducted. Overall, this research offers valuable insights into CAP co-crystal formation with PRO, detailing their solid-state behavior and intermolecular interactions, which could aid in developing new co-crystals with improved pharmaceutical properties.
Published Version
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