X-RAY DIFFRACTION AND VIBRATIONAL SPECTROSCOPIC STUDIES OF THE INTERMOLECULAR INTERACTIONS ON THE GRINDING AND COMPACTION BEHAVIOURS OF LOPINAVIR AND RITONAVIR CRYSTALS

Lopinavir (LPV) and ritonavir (RTV) are anti-viral drugs used in combination and commonly prepared through hot-melt extrusion techniques. Mechanical processes are greatly involved. including blending and milling. Therefore, the crystal behavior of LPV and RTV under the mechanical process is an interesting study. Here, the LPV, RTV, and their mixtures were processed by two different treatments: grinding and compression processes. The solid-state properties of the drugs were evaluated by powder x-ray diffraction (PXRD) differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FUR), Raman spectroscopy. Single-crystal XRD analysis was also carried out to confirm the packing structure in the crystal lattice. It was observed that LPV was very sensitive to the grinding process, where it tends to form an amorphous solid in both the pure and mixture forms. On the other hand, RTV has a very stable crystalline structure and was able to retain its crystallinity even under grinding. Both LPV and RTV were observed to be quite stable under compression. where both retained their crystalline form with only slight changes in their d-spacing values. This study high-lighted the molecular origin of LPV and RTV crystal behavior alter grinding and compression processes.