TY - JOUR
T1 - Geraniol:l-menthol eutectic mixtures; thermophysical properties and drug solubility
AU - Esfahani, Mohammadreza Haftbaradaran
AU - Bergua, Fernando
AU - Delso, Ignacio
AU - Lafuente, Carlos
AU - Artal, Manuela
N1 - Data availability: The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.
PY - 2025/8
Y1 - 2025/8
N2 - The study of eco-sustainable alternative solvents as the eutectic mixtures (ESs) is a fundamental pillar of the concept of green chemistry. Furthermore, the dissolution of pharmaceutical active ingredients (APIs) in ESs has shown to be a feasible strategy to improve the bioavailability of poorly soluble APIs in water. Here, three geraniol:l-menthol (GM) mixtures are characterized for the first time. The structure and thermophysical properties were evaluated and discussed. Furthermore, the ability of GM ES and pure geraniol (G) to dissolve five APIs was determined and compared with that of water and other ESs. No similar studies were found in the literature for this system. From NMR, a more slowly diffusion of the species as the l-menthol ratio increased was observed. All hydrodynamic radii were similar, about 6.8 Å. Also, no strong aggregation was observed. At 298.15 K, the values of density, free volume, and surface tension were about 890 kg/m3, 72 %, and 28.5 mN/m, respectively. The dynamic viscosity ranged from 10 to 19 mPa s. These properties decreased as the G mole ratio increased. Furthermore, a parallel orientation of the adjacent dipoles was observed. Thermodynamic correlations and PC-SAFT equation of state were validated. The lowest solubility was obtained with water as solvent and the highest with pure G. Respectively, the values expressed as mole fraction of API were: 6.12·10−6 and 2.31·10−4 for nitrofurantoin, 4.17·10−6 and 1.69·10−3 for furosemide, 2.56·10−8 and 0.028 for quercetin, 3.08·10−5 and 0.026 for tetracycline, and 7.66·10−7 and 0.042 for carvedilol.
AB - The study of eco-sustainable alternative solvents as the eutectic mixtures (ESs) is a fundamental pillar of the concept of green chemistry. Furthermore, the dissolution of pharmaceutical active ingredients (APIs) in ESs has shown to be a feasible strategy to improve the bioavailability of poorly soluble APIs in water. Here, three geraniol:l-menthol (GM) mixtures are characterized for the first time. The structure and thermophysical properties were evaluated and discussed. Furthermore, the ability of GM ES and pure geraniol (G) to dissolve five APIs was determined and compared with that of water and other ESs. No similar studies were found in the literature for this system. From NMR, a more slowly diffusion of the species as the l-menthol ratio increased was observed. All hydrodynamic radii were similar, about 6.8 Å. Also, no strong aggregation was observed. At 298.15 K, the values of density, free volume, and surface tension were about 890 kg/m3, 72 %, and 28.5 mN/m, respectively. The dynamic viscosity ranged from 10 to 19 mPa s. These properties decreased as the G mole ratio increased. Furthermore, a parallel orientation of the adjacent dipoles was observed. Thermodynamic correlations and PC-SAFT equation of state were validated. The lowest solubility was obtained with water as solvent and the highest with pure G. Respectively, the values expressed as mole fraction of API were: 6.12·10−6 and 2.31·10−4 for nitrofurantoin, 4.17·10−6 and 1.69·10−3 for furosemide, 2.56·10−8 and 0.028 for quercetin, 3.08·10−5 and 0.026 for tetracycline, and 7.66·10−7 and 0.042 for carvedilol.
KW - Eutectic solvents
KW - Geraniol
KW - L-menthol
KW - Solubility active pharmaceutical ingredients
KW - Thermophysical properties
UR - https://www.scopus.com/pages/publications/105007710803
U2 - 10.1016/j.scp.2025.102070
DO - 10.1016/j.scp.2025.102070
M3 - Article
AN - SCOPUS:105007710803
SN - 2352-5541
VL - 46
JO - Sustainable Chemistry and Pharmacy
JF - Sustainable Chemistry and Pharmacy
M1 - 102070
ER -