Cocrystallization of lenvatinib and temozolomide to improve the performance in terms of stability, dissolution, and tabletability

Abstract

Two anti-melanoma drugs, lenvatinib and temozolomide, were cocrystallized to obtain two drug–drug cocrystal solvates, TMZ–LEN·MeOH (1 : 1 : 1) and TMZ–LEN·EtOH (1 : 1 : 1). They were fully characterized by XRD and thermal analyses, NMR and FTIR spectroscopy. The crystal structure of TMZ–LEN·MeOH shows that LEN is simultaneously linked to TMZ and methanol via hydrogen bonding interactions. Stability, dissolution and compaction evaluations highlight that the formation of the drug–drug cocrystal not only improves the physicochemical stability and tabletability of TMZ, but also optimizes the dissolution behavior of LEN and TMZ, respectively. Therefore, TMZ–LEN·MeOH and TMZ–LEN·EtOH have great potential to be developed as a drug combination, which will address the problematic properties of LEN and TMZ, for the treatment of melanoma patients with brain metastases.