Polymorphism of anti-HIV drug efavirenz: Investigations on thermodynamic and dissolution properties

Abstract

Polymorphs, cocrystals, solvates, and hydrates have been reported for efavirenz (EFV), which is part of high activity antiretroviral therapy (HAART), and it is considered to be the best choice in the treatment of adults and children. However, studies about thermodynamic stability and improvement of dissolution properties have been rarely reported for the anhydrous polymorphic forms. Therefore, the aim of this work was to characterize the solid state of anhydrous polymorph I and polymorph II (herein obtained), to study the thermodynamic stability and strategies to improve the dissolution properties. In addition, techniques such as, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), hot stage microscopy (HSM), scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), raman spectroscopy (RS), theoretical calculations, and solid-state nuclear magnetic resonance (ss-NMR) were used to complete this work. Thermodynamic studies showed that polymorphs I and II are enantiotropically related with the isoenergetic point between 35 and 40 °C. The EFV polymorph II showed itself to be more stable and 10-fold more soluble than polymorph I, due to modifications of morphology. Therefore, polymorph II could be an excellent candidate with significant advantages for pharmaceutical formulations.