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

Abstract

Objective: In 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). Methods: Thermal 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. Results: Eutectic 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. Conclusion: Mechanochemistry 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.