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

• Published in: CrystEngComm Vol. 25; no. 29; pp. 4189 - 4198
• Main Authors: Wang, Zhi-Qing, Dai, Xia-Lin, Gu, Dai-Lin, Wu, Chao, Lu, Tong-Bu, Long, Xiang-Tian, Chen, Jia-Mei
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 24.07.2023
• Subjects: Crystal structure; Dissolution; Hydrogen bonding; NMR; Nuclear magnetic resonance; Stability analysis
• ISSN: 1466-8033; 1466-8033
• DOI: 10.1039/d3ce00473b

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. Cocrystallization of two anti-melanoma drugs, lenvatinib and temozolomide, resulted in two drug-drug cocrystal solvates presenting improved performance in terms of stability, dissolution, and tabletability, which show great potential to be developed as a drug combination.