Mechanochemical synthesis and characterization of Zidovudine-lamivudine solid dispersion (binary eutectic mixture)

Abstract

ObjectiveIn the present work, solid-state co-grinding also known as mechanochemistry is employed to investigate the co-crystal formation between two HIV nucleoside reverse transcriptase inhibitors lamivudine (3TC) and zidovudine (AZT). MethodsThermal analyses by DSC, HSM, and TGA provided thermodynamic parameters of the samples over the heating exercise. Infrared spectroscopy enabled the evaluation of structural information of LMZT (1:1) sample while its morphology was assessed using Scanning electron microscopy. Powder X-ray diffraction analysis confirmed the sample's identity. ResultsEutectic LMZT (1:1) was obtained from co-grinding. Its lower melting transition compared to pure lamivudine and zidovudine was confirmed by HSM and DSC. Scanning electron microscopy micrographs indicated that the LMZT (1:1) sample exhibits irregular, round-shaped particles with smooth surfaces. Infrared spectroscopy revealed weak interactions between 3TC and AZT and Powder X-rays diffraction pattern that's made of a summation of pure APIs diffraction peaks, confirming LMZT (1:1) as a eutectic mixture. Solubility at 37 °C, in different buffered solutions to mimic gastrointestinal, was established and the measurement by HPLC indicated that LMZT (1:1) dual-API solid dispersion exhibited enhanced solubility for both active pharmaceutical ingredients. ConclusionMechanochemistry is a potential and green method for co-crystal synthesis. Co-crystal formation attempt between 3TC and AZT, using solid-state co-grinding resulted into a eutectic LMZT (1:1). Characterization revealed a lower melting transition, enhanced solubility and a good dissolution profile associated with the resultant eutectic, making this an interesting dual-API delivery system. Further studies should highlight the stability and antiviral activity of this combination.