Investigation of moricizine hydrochloride polymorphs.
The antiarrhythmic agent moricizine hydrochloride exhibits a single melting-decomposition endotherm peak at temperatures ranging from 209 to 214.5 degrees C (Form I) when recrystallized from polar solvents, as determined by differential scanning calorimetric analysis. However, a different polymorphic form (Form II), with a differential scanning calorimetric melting-decomposition peak temperature of 190 degrees C, was generated by recrystallizing moricizine hydrochloride from nonpolar solvents. These two polymorphic forms can be reversibly converted to one another by selecting recrystallization solvents. The existence of these polymorphs was confirmed by Fourier transform IR microscopy, X-ray powder diffractometry, and solution calorimetry. Polymorphic Form I exhibited a slightly slower initial dissolution rate than Form II, which correlated well with heats of solution data (less heat needed to dissolve Form II). A simulated wet granulation process did not change the polymorphic form, suggesting that wet granulation is feasible for tablet preparation.
Wu
L S
LS
DuPont Merck Pharmaceutical Company, Wilmington, DE 19880-0400.
Torosian
G
G
Sigvardson
K
K
Gerard
C
C
Hussain
M A
MA
D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003460:Crystallization; D016293:Moricizine / Q000737:chemistry*; D012995:Solubility; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D014961:X-Ray Diffraction
D012997:Solvents; D016293:Moricizine