Characterization of nicergoline polymorphs crystallized in several organic solvents.
Nicergoline (NIC), a poorly water-soluble semisynthetic ergot derivative, was crystallized from several organic solvents, obtaining two different polymorphic forms, the triclinic form I and the orthorhombic form II. NIC samples were then characterized by several techniques such as (13)C cross-polarization magic angle spinning solid-state spectroscopy, room-temperature and high-temperature X-ray powder diffraction, differential scanning calorimetry, and by analysis of weight loss, solvent content, powder density, morphology, and particle size. Solubility and intrinsic dissolution rates determined for the two polymorphic forms in water and hydrochloride solutions (HCl 0.1 N) were always higher for form II than for form I, which is actually the form used for the industrial preparation of NIC medicinal products. Preformulation studies might encourage industry for the evaluation of polymorph II, as it is more suitable for pharmaceutical applications. Results in drug delivery, as well as those obtained by the above-mentioned techniques, and the application of Burger-Ramberger's rules make it possible to conclude that there is a thermodynamic relation of monotropy between the two polymorphs. This last assumption may help formulators in predicting the relative stability of the two forms.
University of Camerino, School of Pharmacy, Camerino, Italy.
Ledjan
L
Malaj
Roberta
R
Censi
Doretta
D
Capsoni
Luca
L
Pellegrino
Marcella
M
Bini
Stefania
S
Ferrari
Roberto
R
Gobetto
Vincenzo
V
Massarotti
Piera
P
Di Martino
D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002849:Chromatography, Gas; D003460:Crystallization; D018360:Crystallography, X-Ray; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D009530:Nicergoline / Q000737:chemistry*; D010316:Particle Size; D033362:Powder Diffraction; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature
D012997:Solvents; D009530:Nicergoline