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Published on: August 9, 2022
Conformational polymorphism in aripiprazole: Preparation, stability and structure of five modifications
Doris E Braun1, Thomas Gelbrich, Volker Kahlenberg
1Institute of Pharmacy, University of Innsbruck, Innrain 52, 6020 Innsbruck, Austria.
Journal of Pharmaceutical Sciences
|November 15, 2008
Summary
Five aripiprazole polymorphs were identified, revealing distinct crystal structures and thermodynamic relationships. Three metastable forms show high kinetic stability, making them promising for solid dosage form development.
Area of Science:
- Pharmaceutical Sciences
- Solid-State Chemistry
- Crystallography
Background:
- Aripiprazole is a crucial antipsychotic medication.
- Understanding its polymorphic forms is vital for drug formulation and efficacy.
- Polymorphism significantly impacts drug solubility, stability, and bioavailability.
Purpose of the Study:
- To prepare and characterize phase-pure aripiprazole polymorphs.
- To elucidate the thermodynamic relationships and stability of different crystalline forms.
- To assess the suitability of polymorphs for pharmaceutical development.
Main Methods:
- Preparation and characterization of five aripiprazole modifications.
- Techniques included thermal analysis, vibrational spectroscopy, and X-ray diffractometry.
- Thermodynamic relationships were determined using thermochemical data and Hirshfeld surface analysis.
Main Results:
- Five distinct aripiprazole polymorphs were successfully prepared and characterized.
- Thermodynamic analysis revealed enantiotropic and monotropic relationships between polymorphs.
- Specific temperature ranges were identified for the thermodynamic stability of forms I, II, and X degrees.
- Crystal structures (triclinic, monoclinic, orthorhombic) and molecular conformations varied among polymorphs.
- Three metastable polymorphs exhibited high kinetic stability.
Conclusions:
- The study provides a comprehensive understanding of aripiprazole polymorphism.
- Identified stable and metastable forms offer insights for targeted drug design.
- The kinetically stable polymorphs are suitable candidates for developing effective solid dosage forms.
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