Crystallization of probucol from solution and the glassy state

Area of Science:

• Solid-state chemistry
• Materials science
• Pharmaceutical science

Background:

• Probucol (PBL) is a drug with known polymorphic forms.
• Understanding crystallization behavior is crucial for drug stability and formulation.

Purpose of the Study:

• To investigate the crystallization of probucol (PBL) from solution and glassy states.
• To identify and characterize novel crystal forms of PBL.
• To determine the thermodynamic relationships between different PBL polymorphs.

Main Methods:

• Solution crystallization using six solvents and three methods (evaporation, solvent addition, cooling).
• Isothermal crystallization studies of PBL glass.
• Thermodynamic analysis of crystal form relationships.

Main Results:

• Identified four crystal forms of PBL: forms I, II, III, and a cyclohexane-solvate.
• Determined that forms I and II are likely enantiotropically related with a transition below 5°C.
• Observed that PBL glass crystallizes into form III (25-50°C) then transforms to form I.
• Established that PBL crystallization is pressure-controlled, indicating enhanced glass stability.

Conclusions:

• Isothermal crystallization is effective for discovering uncommon PBL crystal forms.
• The pressure-controlled nature of PBL crystallization contributes to its high physical glass stability.