Thermodynamic study on solubility of brain tumor drug in supercritical solvent: Temozolomide case study

Abstract

One of the effective medications for Glioblastoma Multiforme is Temozolomide (TMZ) which is taken as a treatment for some brain cancers. With respect to the importance of this drug in cancer therapy, the solubility of this medicine was analyzed under various ranges of pressure and temperature in supercritical carbon dioxide (SC-CO2) to evaluate the possibility of drug micronization for reducing its undesired side effects. The measurements were conducted using gravimetric method and revealed that the solubility of the drug is between 4.30 × 10−4 to 5.28 × 10−3 based on mole fraction. The results demonstrated the strong dependency of the TMZ solubility to pressure and temperature, while the effect of pressure is more profound at higher temperatures. Besides, the calculated solubility data was correlated employing five popular semi-empirical density-based correlations including Bartle et al., Chrastil, Kumar and Johnston, Mendez-Santiago-Teja, and Garlapati & Madras models. The obtained outcomes illustrated that among the tested models, KJ led to the best correlative ability with average absolute relative deviation percent (AARD %) of 8.39%, while Garlapati and Madras led to the worst modeling results with AARD % of 15.20%.