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An insight into thermodynamic relationship between polymorphic forms of efavirenz
Renu Chadha1, Poonam Arora, Anupam Saini
1University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India. renukchadha@rediffmail.com
Summary
This study identified six polymorphic forms of efavirenz, revealing thermodynamic relationships and transformations between them. Form I is the most stable, while other forms exhibit monotropy and enantiotropy.
Area of Science:
- Solid-state chemistry
- Pharmaceutical sciences
- Materials science
Background:
- Polymorphism significantly impacts drug efficacy and stability.
- Understanding efavirenz polymorphism is crucial for its pharmaceutical development.
Purpose of the Study:
- To investigate the crystallization of efavirenz and identify its polymorphic forms.
- To characterize the thermal behavior and inter-conversion of these forms.
- To determine the free energy and thermodynamic relationships between efavirenz polymorphs.
Main Methods:
- Slow crystallization from various solvents under controlled conditions.
- Thermogravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC) for thermal analysis.
- Solution calorimetry and solubility studies to determine transition temperatures.
Main Results:
- Six distinct polymorphic forms of efavirenz were identified and fully characterized.
- No hydrates or solvates were detected.
- Thermally induced transformations were observed, with five forms (II-VI) being metastable.
- Four polymorphic pairs exhibited monotropic relationships, and one pair (VIL/VIH) demonstrated enantiotropy.
- Form I was identified as the most thermodynamically stable but least soluble form.
Conclusions:
- Efavirenz exhibits complex polymorphism with both monotropic and enantiotropic relationships.
- Thermodynamic data, including transition temperatures, are essential for understanding polymorphic behavior.
- The study provides critical thermodynamic insights into efavirenz polymorphs, aiding in formulation development.
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