Dual-drug co-crystal synthesis for synergistic in vitro effect of three key first-line antiretroviral drugs

Abstract Two pharmaceutical solid state co-crystals EFZA and NEF of two non-nucleoside reverse transcriptase inhibitors (efavirenz, EFV and nevirapine, NVP) and a nucleoside reverse transcriptase inhibitor, zidovudine (AZT) were prepared. Currently, these drugs are essential in various front-line HIV treatment regimens due to their potential in the management of HIV infection. Solid-state principles and solvent-assisted grinding were used for screening of co-crystal preparation. Characterization was carried out using DSC, HSM and TGA, then complimented by FT-IR spectral data and powder X-ray diffraction. HPLC analysis was used for a solubility assays. Both co-crystals indicated different thermal behaviour compared to the individual drug components. Differences in vibrational modes within the spectral region and the unique powder X-ray patterns confirmed the identity of EFZA and NEF as new molecular derivatives. Quantitative studies using HPLC indicated an enhanced solubility of the co-crystals at different pH values compared to the parent compounds; thus making these interesting candidates for future formulation.