Über polymorphe Modifikationen des Nifedipine aus unterkühlten Schmelzen

Abstract

Nifedipine bildet in unterkiihlten Schmelzen zwei neue Modifikationen: Eine bei 162O-164O schmelzende Modifikation I1 (feinstrahlige Aggregate) sowie eine weitere polymorphe Modifikation I11 (balkenformiger Kristallhabitus), die zwischen 134O-137O schmilzt.

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

“…1) is a waterinsoluble drug acting as a calcium channel antagonist, extensively used for the treatment of various cardio-vascular disorders (Fleckenstein, 1977;Sorkin et al, 1985;Ali, 1989). Nifedipine polymorphism has been subject to detailed studies and was first described by Eckert & Mueller (1977), who report the existence of three monotropically related polymorphs, namely modifications (I), (II) and (III); modification (I) (form A) is stable at room temperature, while modification (II) (form B) and (III) (form C) are metastable and typically obtained from supercooling of the melt and subsequent annealing. The stable modification is that used in pharmaceutical formulations, while the other two polymorphs may appear as by-products of the fabrication process, especially when the presence of carrier molecules such as cyclodextrins or polyvinylpyrrolidone is involved (Uekama et al, 1992;Hirayama et al, 1994).…”

Preparation and Transformation of True Nifedipine Polymorphs: Investigated with Differential Scanning Calorimetry and X-Ray Diffraction Pattern Fitting Methods

“…[1][2][3] Most studies dealing with the polymorphic transformations of nifedipine focused on the stability of the amorphous form and the factors that may induce its transformation. [4][5][6] For example, the effect of excipients such as cyclodextrin and poly(vinylpyrrolidone) (PVP) and processing such as spray drying on the stability of the amorphous state when exposed to increased temperature and humidity.…”

Crystallization Kinetics of Amorphous Nifedipine Studied by Model-Fitting and Model-Free Approaches

“…The crystallization kinetics of amorphous nifedipine (4‐(2‐nitrophenyl)‐2,6‐dimethyl‐3,5‐dicarbomethoxy‐1,4‐dihydropyridine), which is a calcium channel blocker used in the treatment of cardiovascular diseases, was studied in this work. Three monotropically related polymorphic forms of nifedipine have been described 32,33. The commercial form, modification I, with a melting point of 169–172°C, is the most stable polymorph known today.…”

“…The commercial form, modification I, with a melting point of 169–172°C, is the most stable polymorph known today. The metastable polymorphs II and III have melting points of 161–163 and 135°C, respectively 32,33. Various solvates of nifedipine have also been reported 33…”