X-ray diffraction and vibrational spectroscopic studies of the intermolecular interactions on the grinding and compaction behaviours of lopinavir and ritonavir crystals

Abstract

Lopinavir (LPV) and ritonavir (RTV) are anti-viral drugs used in combination and commonly pre-pared through hot-melt extrusion techniques. Mechanical processes are greatly involved, including blendingand milling. Therefore, the crystal behavior of LPV and RTV under the mechanical process is an interestingstudy. Here, the LPV, RTV, and their mixtures were processed by two different treatments: grinding and com-pression processes. The solid-state properties of the drugs were evaluated by powder x-ray diffraction (PXRD)differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy.Single-crystal XRD analysis was also carried out to confirm the packing structure in the crystal lattice. It wasobserved that LPV was very sensitive to the grinding process, where it tends to form an amorphous solid in boththe pure and mixture forms. On the other hand, RTV has a very stable crystalline structure and was able to retainits 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 after grinding and compression processes.

Yuda Prasetya Nugraha

Assistant Professor & Researcher in Pharmaceutics

My research interests include structure-property relationship, solid-state characterization of drugs, and solid dosage form developement.