Solid state characterization of azelnidipine-oxalic acid co-crystal and co-amorphous complexes: The effect of different azelnidipine polymorphs

In present study, based on the two polymorphs (alpha and beta form) of azelnidipine (AZE), 12 complexes of AZE and oxalic acid (OXA) were prepared by solvent-assisted grinding (SG) and neat powder grinding (NG) methods at the AZE/OXA molar ratios of 2:1, 1:1, and 1:2. The effect of the different polymorphs of AZE on the micro-structure of the complexes were investigated by powder X-ray diffraction (PXRD), tempreture modulated differential scanning calorimetry and thermogravimetric analysis, cryo-field emission scanning electron microscope system, fourier transform infrared (FTIR), and solid-state nuclear magnetic resonance spectroscopy. beta-AZE-OXA co-crystal was produced at beta-AZE/OXA molar ratio of 2:1 when SG method was used; while alpha-AZE was used to produce alpha-AZE-OXA co-crystal at same condition. However, the other 10 combinations were in co-amorphous forms, including the NG samples with alpha (or beta)-AZE/OXA molar ratios of 2:1, 1:1 (SG and NG), and 1:2 (SG and NG). Although the XRD pattern and IR spectra of the two co-crystals showed no difference, the melting enthalpy and specific heat c(p) of the beta-AZE-OXA co-crystal was higher than that of the alpha-AZE-OXA co-crystal, indicating that the numbers of solvent molecules which entered the two co-crystal lattices were different. Interestingly, obvious difference occurred in the IR spectra between the alpha-AZE-OXA and beta-AZE-OXA co-amorphous systems. 1745 cm(-1) wave-numbers, which were assigned to the free C=O groups, appeared in the alpha-AZE-OXA co-amorphous systems even when just a small amount of OXA was introduced, thereby indicating the presence of different intermolecular forces in the two series of co-amorphous forms. The solubility in different media and the dissolution rate in 0.1 mol L-1 HCl of the 12 complexes were determined. The dramatically improved dissolution rates of the alpha- and beta-AZE-OXA 1:2 (NG) combinations in vitro showed potential in improving the physicochemical properties of AZE by co-amorphous complex formation. (C) 2017 Elsevier B.V. All rights reserved.