Determination of the crystal structure of nifedipine form C by synchrotron powder diffraction

Abstract

The crystal structure of the metastable form C polymorph of nifedipine [C(17)H(18)N(2)O(6), 3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate] was determined by means of direct-space techniques applied to high-resolution synchrotron powder diffraction data. The polymorph crystallizes in the space group P1 and exhibits a molecular packing significantly different from that of the stable modification, with molecules aligned in an orthogonal configuration inside the unit cell. The molecular conformation, on the other hand, remains substantially unmodified between the two polymorphs. Additionally, in situ thermal characterization of nifedipine crystallization behaviour was performed, confirming the nucleation of another metastable polymorph (form B) prior to the complete crystallization of the stable modification. A complete structural characterization of form B was not possible owing to its very limited stability interval.

Nanoconfinement Effects on the Glass Transition and Crystallization Behaviors of Nifedipine

“…The PXRD results for the as-received sample and quenched sample are shown in Figure , together with other samples isothermally crystallized (Curves C to E), and which will be discussed in the section on crystallization. The diffraction pattern for the as-received NIF (Curve A in Figure ) agrees with the NIF form A reported in the literature, − indicating that the as-received sample is pure crystalline NIF form A. The bulk (Curve B) and 12 nm confined NIF (Curve D) after melting and quenching show a typical amorphous pattern, indicating that both for bulk and nanoconfined NIF, the material formed by quenching is amorphous NIF.…”

Isothermal Crystallization and Time–Temperature Transformation of Amorphous Nifedipine: A Case of Polymorphism Formation and Conversion

“…It is known that NIF has multiple polymorphs. The most stable polymorph is the α-form (also denoted as form A and form I, T m = 170–172 °C), and it has been reported that two other metastable polymorphs can form: β (II/B, T m = 160–163 °C) and γ (III/C T m = 133–135 °C). − Several studies have also reported other metastable polymorphs ,, that are unstable and convert quickly into one of the other more stable forms. In addition, we have observed evidence of a polymorph that was observed only upon nanoconfinement between 50 and 200 nm .…”

Structure determination of three polymorphs of xylazine from laboratory powder diffraction data

“…Metastable forms are known to crystallize as polymorphic impurities in the manufacturing of pharmaceutical solids where stable forms are desired (Grant, 1999). The crystal structures of polymorphs and their determination are among the main topics of crystallization research (Morissette et al, 2004;Bortolotti et al, 2011).…”