X-RAY STRUCTURAL STUDIES OF LOMERIDINE DIHYDROCHLORIDE POLYMORPHS

Two polymorphs (forms I and II) of lomeridine dihydrochloride henyl)me thyl]-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride) were prepa red and characterized by means of X-ray powder diffractometry, infrare d spectroscopy (IR), thermal analysis, and moisture absorption equilib rium. The molecular structures and/or molecular conformations of the t wo polymorphs were determined by three-dimensional X-ray analysis. Eac h polymorph formed two hydrogen bonds between the two hydrochloric aci ds and the two nitrogen atoms of piperazine (N1, N4). In form I, the N 1-chloride ion distance (2.98 Angstrom) was almost same as the N4-chlo ride ion distance (2.99 Angstrom). In form II, the N1-chloride ion dis tance (2.95 Angstrom) was shorter than the N4-chloride ion distance (3 .06 Angstrom). The IR spectra showed an absorption band assigned to th e NH stretching vibration of form I centered at 2361 and that of form II split into two peaks at 2186 cm(-1) and 2560 cm(-1). The differenti al thermal analysis (DTA) profiles showed that both form I and form II have an endothermic peak which would relate to the release of hydroch loric acid. The temperature of the peak in form I was higher than that in form II. The differences in the two hydrogen bond lengths of form II appear to be reflected in these IR and DTA profiles. The hygroscopi c behavior of forms I and II was investigated at various relative humi dities at 25 degrees C. Form II has a constant molecular composition o nly between 20 and 51% relative humidity(RH). On the other hand, form I has an anhydrate form between 0 and 64% RH. Accordingly, form II is not appropriate for pharmaceutical preparations, in contrast to form I .