RESUMEN
In this study, both practical and theoretical aspects of the solubility of edaravone (EDA) in Deep Eutectic Solvents (DESs) were considered. The solubility of edaravone in some media, including water, can be limited, which creates the need for new efficient and environmentally safe solvents. The solubility of EDA was measured spectrophotometrically and the complex intermolecular interactions within the systems were studied with the COSMO-RS framework. Of the four studied DES systems, three outperformed the most efficient classical organic solvent, namely dichloromethane, with the DES comprising choline chloride and triethylene glycol, acting as hydrogen bond donor (HBD), in a 1:2 molar proportion yielding the highest solubility of EDA. Interestingly, the addition of a specific amount of water further increased EDA solubility. Theoretical analysis revealed that in pure water or solutions with high water content, EDA stacking is responsible for self-aggregation and lower solubility. On the other hand, the presence of HBDs leads to the formation of intermolecular clusters with EDA, reducing self-aggregation. However, in the presence of a stoichiometric amount of water, a three-molecular EDA-HBD-water complex is formed, which explains why water can also act as a co-solvent. The high probability of formation of this type of complexes is related to the high affinity of the components, which exceeds all other possible complexes.
RESUMEN
This study explores the edaravone solubility space encompassing both neat and binary dissolution media. Efforts were made to reveal the inherent concentration limits of common pure and mixed solvents. For this purpose, the published solubility data of the title drug were scrupulously inspected and cured, which made the dataset consistent and coherent. However, the lack of some important types of solvents in the collection called for an extension of the available pool of edaravone solubility data. Hence, new measurements were performed to collect edaravone solubility values in polar non-protic and diprotic media. Such an extended set of data was used in the machine learning process for tuning the parameters of regressor models and formulating the ensemble for predicting new data. In both phases, namely the model training and ensemble formulation, close attention was paid not only to minimizing the deviation of computed values from the experimental ones but also to ensuring high predictive power and accurate solubility computations for new systems. Furthermore, the environmental friendliness characteristics determined based on the common green solvent selection criteria, were included in the analysis. Our applied protocol led to the conclusion that the solubility space defined by ordinary solvents is limited, and it is unlikely to find solvents that are better suited for edaravone dissolution than those described in this manuscript. The theoretical framework presented in this study provides a precise guideline for conducting experiments, as well as saving time and resources in the pursuit of new findings.
RESUMEN
INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia, increasing the risk of stroke and all-cause mortality. Pulmonary vein isolation (PVI) with cryoballoon ablation (CBA) is a widely accepted approach for invasive treatment of patients with AF. CBA effectiveness is considered to be strongly dependent upon the anatomy of pulmonary veins, mainly the ovality of pulmonary veins' ostia. However, most published results refer to the second-generation cryoballoon. AIM: To investigate the impact of the ovality index (OI) of pulmonary veins (PVs) on cryokinetic parameters and acute effectiveness of PVI with the third-generation cryoballoon catheter. MATERIAL AND METHODS: We enrolled 54 patients with documented drug-refractory, symptomatic paroxysmal and persistent AF, who underwent CBA with the third-generation cryoballoon between March 2019 and July 2020. Prior to the procedure all patients underwent computed tomography (CT) scans to evaluate anatomy of PVs and calculate the ovality indices for each vein. Analyzed patients were divided into two equal groups depending on the mean OI for all veins. RESULTS: No differences were observed in acute effectiveness, total procedure time, freeze time, need for additional applications and complications in the group with lower (OI < 1.27) and higher (OI > 1.27) OI values. Remarkably, fluoroscopy time was even slightly shorter (p = 0.046) in patients with high OI. CONCLUSIONS: In the analyzed population, increased pulmonary vein OI had no negative effect on the CBA procedure performed with the third-generation cryoballoon catheter; therefore it can be considered as a more comprehensive single-shot PVI tool.