Related Experiment Videos
Polymorphism and preformulation studies of lifibrol.
1University of Innsbruck, Institute of Pharmacognosy, Innsbruck, Austria. artur.burger@uibk.ac.at
Summary
Three polymorphic forms of the cholesterol-lowering drug lifibrol were identified and characterized. These distinct lifibrol modifications exhibit varying densities, solubilities, and crystal habits, impacting tablet pressing properties.
Area of Science:
- Pharmaceutical Sciences
- Solid-State Chemistry
Background:
- Lifibrol is a novel drug substance developed for cholesterol lowering.
- Understanding the polymorphic forms of active pharmaceutical ingredients (APIs) is crucial for drug development and manufacturing.
Purpose of the Study:
- To detect, investigate, and characterize the polymorphic modifications of lifibrol.
- To determine the physical and chemical properties of each lifibrol modification.
Main Methods:
- Thermomicroscopy
- Differential Scanning Calorimetry (DSC)
- Infrared (IR) spectroscopy
- X-ray powder diffractometry
- Density measurements
- Solubility studies (temperature and pH dependence)
- Behavior under humid air
Main Results:
- Three polymorphic modifications (Mod. I, Mod. II, Mod. III) of lifibrol were identified.
- Mod. I (m.p. 142°C) and Mod. II (m.p. 135°C) are stable and exhibit enantiotropic behavior.
- Mod. III, obtained from glassy melt, is monotropic.
- Distinct differences in IR spectra, density, solubility, and crystal habit (lamellar for Mod. I, rhombohedral for Mod. II) were observed.
- Mod. II showed better predicted tablet pressing properties due to its crystal habit.
Conclusions:
- The three lifibrol polymorphic forms are distinguishable by IR spectroscopy.
- Enantiotropic and monotropic relationships were established between the modifications.
- Differences in physical properties, particularly crystal habit and solubility, have implications for pharmaceutical formulation and manufacturing, with Mod. II showing promise for tablet production.