A Simultaneous Differential Scanning Calorimetry-X-ray Diffraction Study of Olanzapine Crystallization from Amorphous...

Area of Science:

• Materials Science
• Pharmaceutical Science
• Solid-State Chemistry

Background:

• Amorphous solid dispersions (ASDs) enhance drug dissolution but face challenges from drug recrystallization.
• Understanding the mechanisms of polymorph generation in ASDs is crucial for product development.
• Olanzapine (OLZ) polymorphism is complex and influences drug product performance.

Purpose of the Study:

• To investigate the sequential polymorph generation of olanzapine (OLZ) in various polymer dispersions upon heating.
• To utilize combined differential scanning calorimetry (DSC) and synchrotron X-ray diffraction for detailed analysis.
• To elucidate the complex interconversions and relative proportions of polymorphs as a function of temperature.

Main Methods:

• Preparation of amorphous solid dispersions (ASDs) of olanzapine (OLZ) in poly(lactide-co-glycolide) (PLGA), polylactide (PLA), and hydroxypropyl methyl cellulose acetate succinate (HPMCAS).
• Combined differential scanning calorimetry (DSC) and synchrotron X-ray diffraction (XRD) to monitor phase transitions.
• Heating experiments to track the formation and interconversion of OLZ polymorphs and solvates.

Main Results:

• Spray-dried OLZ with HPMCAS formed an ASD, yielding forms I and IV upon heating.
• Dispersions in PLGA and PLA initially contained amorphous OLZ and a dichloromethane solvate.
• Upon heating, amorphous OLZ converted to forms I, II, and IV, while the solvate transformed into forms I and II.
• Quantitative assessment of polymorph generation sequences and proportions was achieved, revealing complexities beyond DSC alone.

Conclusions:

• The sequence of polymorph generation in OLZ dispersions is complex and temperature-dependent.
• Combined DSC-XRD provides a more comprehensive understanding of solid-state transformations than DSC alone.
• This approach aids in identifying the full range of polymorphic forms a drug molecule can produce, crucial for pharmaceutical development.