Pressure-temperature state diagram for the phase relationships between benfluorex hydrochloride forms I and II: a case of enantiotropic behavior

J Pharm Sci. 2012 Mar;101(3):1073-8. doi: 10.1002/jps.22821. Epub 2011 Nov 18.

Abstract

The active pharmaceutical ingredient racemic benfluorex hydrochloride (benfluorex-HCl) has an interesting phase behavior due to an elusive solid-solid phase transition. The stability hierarchy between different phases is often determined based on heat-related experiments only or slurry interconversion. It is shown that if pressure and volume are taken into account, not only the phase equilibria are correctly positioned in the pressure-temperature phase diagram, but the experimental data also improves. Thus, it has been found that the racemic benfluorex-HCl is enantiotropic under "ordinary conditions" with polymorph II and polymorph I, respectively, being the low- and the high-temperature phases. Above ∼ 151 MPa, the system becomes monotropic and polymorph II is the single stable phase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallization
  • Drug Stability
  • Fenfluramine / analogs & derivatives*
  • Fenfluramine / chemistry
  • Hypolipidemic Agents / chemistry*
  • Phase Transition
  • Pressure
  • Temperature

Substances

  • Hypolipidemic Agents
  • Fenfluramine
  • benfluorex