A Novel Temozolomide-Myricetin Drug-Drug Cocrystal: Preparation, Characterization, Property Evaluations

• Published in: Pharmaceutics Vol. 17; no. 7; p. 906
• Main Authors: Qin, Hai-Xin, Wang, Jie, Peng, Jia-Hui, Dai, Xia-Lin, Li, Cai-Wen, Lu, Tong-Bu, Chen, Jia-Mei
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.07.2025; MDPI
• Subjects: Crystal structure; Crystals; Data collection; Diffraction; Drug therapy; drug-drug cocrystal; Drugs; Flavonoids; Fourier transforms; Glioma; Gliomas; Health aspects; Humidity; Hydrogen; Hydrogen bonding; Infrared spectroscopy; myricetin; Pharmaceuticals; Physicochemical properties; Radiation; Software; Spectrum analysis; stability; Structure; tabletability; Temozolomide; X-rays; China; Germany; Tianjin China; Shanghai China; temozolomide; myricetin; tabletability; drug-drug cocrystal; dissolution; crystal structure; stability
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics17070906

Objectives: Drug-drug cocrystals with improved properties can be used to facilitate the development of synergistic therapeutic combinations. The goal of the present study is to obtain novel drug-drug cocrystals involving two anti-glioma agents, temozolomide (TMZ) and myricetin (MYR). Methods: The novel TMZ-MYR cocrystal was prepared via slurry and solvent evaporation techniques and characterized by X-ray diffraction, thermal analysis, infrared spectroscopy, and dynamic vapor sorption measurements. The stability, compaction, and dissolution properties were also evaluated. Results: Crystal structure analysis revealed that the cocrystal lattice contains two TMZ molecules, one MYR molecule, and four water molecules, which are linked by hydrogen bonding interactions to produce a three-dimensional network. The cocrystal hydrate exhibited favorable stability and tabletability compared to pure TMZ. A dissolution study showed that the maximum solubility of MYR in the cocrystal (176.4 μg/mL) was approximately 6.6 times higher than that of pure MYR·H2O (26.9 μg/mL), while the solubility of TMZ from the cocrystal (786.7 µg/mL) was remarkably lower than that of pure TMZ (7519.8 µg/mL). The solubility difference between MYR and TMZ was diminished from ~280-fold to ~4.5-fold. Conclusions: Overall, the TMZ-MYR cocrystal optimizes the stability and tabletability of TMZ and the dissolution behavior of both drugs, offering a promising approach for synergistic anti-glioma therapy with improved clinical potential.