Pharmaceutical cocrystals of Efavirenz: Towards the improvement of solubility, dissolution rate and stability

Abstract

Efavirenz (EFV) is a Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) class of antiretroviral drug that is included in antiretroviral therapy to treat Human Immunodeficiency Virus (HIV) patients to increase the life-span by avoiding them to develop Acquired Immune Deficiency Syndrome (AIDS). One of the major drawbacks of EFV is its solubility in purified water (0.093 mg/L). In the present work, two cocrystals of EFV using tartaric acid (TAR) and adipic acid (ADP) as coformers that are Generally Recognized as Safe (GRAS) are reported. Both the EFV-TAR and EFV-ADP cocrystals were developed using slow solvent evaporation technique and further characterization of developed cocrystal structures was done by Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC) and Powder x-ray diffraction (PXRD) techniques. The SEM photomicrographs indicated that the EFV-TAR cocrystals were in needle shape with smooth surface. Its length ranged from 100 to 300 μm. The EFV-ADP cocrystals were found to be flaky needle shape with rough surface bearing irregular edges whose length ranged about 50-400 μm. The FT-IR spectra of both developed cocrystals confirmed the formation of a hydrogen bond between EFV and coformers by indicating a notable shift in -C=O functional group. The DSC and PXRD studies were further confirmed the successful development of a novel crystalline form (Cocrystal). The solubility (25 ± 0.5 °C) of EFV-TAR and EFV-ADP cocrystals were found to be 163 and 107 μg/mL respectively, whereas pure EFV showed 94 μg/mL. The dissolution rate (37 ± 0.5 °C) of EFV-TAR and EFV-ADP cocrystals in 1% sodium lauryl sulphate (SLS) solution demonstrated 1.4 and 1.2 times increment respectively, compared to the pure EFV. The developed EFV-TAR and EFV-ADP cocrystals were found to stable for 6 months in ambient conditions (25 ± 2 °C, 60 ± 5% relative humidity). © 2021 Elsevier Ltd. All rights reserved.