Polymorphism and preformulation studies of lifibrol

Three polymorphic modifications of lifibrol, a novel cholesterol-lowering drug substance, were detected and thoroughly investigated and characterized by thermomicroscopy, DSC, IR-spectroscopy and X-ray powder diffractometry. Mod. I (m.p. 142 degrees C) and mod. II (m.p. 135 degrees C) are stable. Furthermore, true densities, solubilities as function of temperature and pH-value as well as the behavior of the crystal forms under the influence of humid air were determined. The three modifications show distinct differences by IR-spectroscopy, through which a distinction even is possible. The density of mod. I is lower than that of mod. II. The transition of mod. II into mod. I corresponds to an endothermic reaction; from this it follows, that between mod. I and mod. II enantiotropism exists. Mod. II is at 20 degrees C by about 44% less soluble as mod. I. Mod. III, which only can be produced by crystallizing the glassy solidified melt, has a negative heat of transition. That means that mod. III behaves monotropic with regard to both enantiotropic modifications I and II. Mod. I exists in form of small lamellae, mostly of irregular forms. Mod. II consists of rhombohedron grains. Because of this difference in habit, for mod. II one can predict the best properties in case of pressing tablets. (C) 2000 Elsevier Science B.V. All rights reserved.