title: Solid state characterization of azelnidipine-oxalic acid co-crystal and co-amorphous complexes: The effect of different azelnidipine polymorphs.
abstract: In present study, based on the two polymorphs (α and β 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. β-AZE-OXA co-crystal was produced at β-AZE/OXA molar ratio of 2:1 when SG method was used; while α-AZE was used to produce α-AZE-OXA co-crystal at same condition. However, the other 10 combinations were in co-amorphous forms, including the NG samples with α (or β)-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 cpof the β-AZE-OXA co-crystal was higher than that of the α-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 α-AZE-OXA and β-AZE-OXA co-amorphous systems. 1745cm-1wave-numbers, which were assigned to the free CO groups, appeared in the α-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 0.1molL-1HCl of the 12 complexes were determined. The dramatically improved dissolution rates of the α- and β-AZE-OXA 1:2 (NG) combinations in vitro showed potential in improving the physicochemical properties of AZE by co-amorphous complex formation.
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, 050017, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Pan
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, 050017, China.
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Pang
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, 050017, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lv
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, 050017, China. Electronic address: jingwang@home.ipe.ac.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, 050017, China.
authors.forename: Caiqin
authors.initials: C
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, 050017, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
mesh_terms: D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning / Q000379:methods; D003460:Crystallization / Q000379:methods; D004095:Dihydropyridines / Q000737:chemistry*; D004355:Drug Stability; D019815:Oxalic Acid / Q000737:chemistry*; D033362:Powder Diffraction / Q000379:methods; D011208:Powders / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013816:Thermodynamics; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D004095:Dihydropyridines; D011208:Powders; D012997:Solvents; D001383:Azetidinecarboxylic Acid; D019815:Oxalic Acid; C061679:azelnidipine
keywords: Azelnidipine; Co-amorphous; Co-crystal; Solubility; Tmdsc