ABSTRACT
The poor water solubility of active pharmaceutical ingredients (APIs) is a major challenge in the pharmaceutical industry. Co-solvents are sometimes added to enhance drug dissolution. A novel group of co-solvents, the Deep Eutectic Solvents (DES), have gained interest in the pharmaceutical field due to their good solvent power, biodegradability, sustainability, non-toxicity, and low cost. In this study, we first provide an overview of all the literature solubility studies involving a drug or API + water + DES, which can be a valuable list to some researchers. Then, we analyze these systems with focus on each individual drug/API and provide statistical information on each. A similar analysis is carried out with focus on the individual DESs. An investigation of the numeric values of the water-solubility enhancement by the different DESs for various drugs indicates that DESs are indeed effective co-solvents, with varying degrees of solubility enhancement, even up to 15-fold. This is strongly encouraging, indicating the need for further studies to find the most promising DESs for solubility enhancement. However, time-consuming and costly trial and error should be prevented by first screening, using theoretical-based or thermodynamic-based models. Based on this conclusion, the second part of the study is concerned with investigating and suggesting accurate thermodynamic approaches to tackle the phase equilibrium modeling of such systems. For this purpose, a large data bank was collected, consisting of 2009 solubility data of 25 different drugs/APIs mixed with water and 31 different DESs as co-solvents at various DES concentrations, over wide ranges of temperatures at atmospheric pressure. This data bank includes 107 DES + water + drug/API systems in total. The solubility data were then modeled according to the solid-liquid equilibrium framework, using the local composition activity coefficient models of NRTL, and UNIQUAC. The results showed acceptable behavior with respect to the experimental values and trends for all of the investigated systems, with AARD% values of 9.65 % and 14.08 % for the NRTL and UNIQUAC models, respectively. In general, the lower errors of NRTL, as well as its simpler calculation process and the requirement of fewer component parameters, suggest the priority of NRTL over UNIQUAC for use in this field.
Subject(s)
Deep Eutectic Solvents , Water , Solubility , Solvents , ThermodynamicsABSTRACT
Short-chain fatty acids are metabolites widely presented in many natural sources, including human feces and blood. Estimation of their composition is a common procedure, usually performed using nuclear magnetic resonance or gas chromatography with a flame ionization detector. However, the commonly used methods often depend on specific sample preparation, such as filtration and homogenization. The gas-chromatography/mass-spectrometry (GC/MS) method with headspace extraction allows sample preparation to be kept to a minimum regardless of the physical state of the sample, which can be potentially useful in metabolomics research of complex natural samples such as blood or feces. In this work, we have demonstrated the applicability of Headspace GC-MS for estimating short chain fatty acid (SCFA) composition. The main problem here is the complex, non-linear dependence between the composition of the compounds in the source phase and the relative pressures in the vapor phase, which are directly measured by this method. We have implemented a thermodynamic model that performs the reverse transformation of relative abundances in the vapor phase to relative concentrations in the liquid phase, and have tested it on some synthetic SCFA mixtures. The developed method is available as a pip package called UniqPy and can be used to describe liquid-vapor equilibrium for any multicomponent system if a sufficient amount of training data is provided. The gas chromatography method with headspace extraction in conjunction with the UniqPy data transformation showed satisfactory quantification accuracy for propionic acid, butyric acid, isobutyric acid, and valeric acid (R-squared > 0.96). The applicability of the method was additionally demonstrated on a series of fecal samples.
Subject(s)
Fatty Acids, Volatile , Metabolomics , Fatty Acids/analysis , Fatty Acids, Volatile/analysis , Feces/chemistry , Flame Ionization , Gas Chromatography-Mass Spectrometry/methods , Humans , Metabolomics/methodsABSTRACT
A new, natural, hydrophobic deep eutectic solvent (NADES) based on DL-menthol and palmitic acid is adopted for the extraction of alcohols from aqueous phase. DL-menthol is used as a hydrogen bond acceptor and palmitic acid, being a natural organic acid, as a hydrogen bond donor. The synthesis is carried out by the addition of DL-menthol and palmitic acid in a defined molar ratio. Physical properties of NADES along with water stability are then measured. Liquid-liquid equilibria (LLE) of lower alcohols, namely, DES (1) + lower alcohols (ethanol/1-propanol/1-butanol) (2) + water (3) are carried out at p = 1 atm and T = 298.15 K. LLE results show type-I phase behavior, where alcohol is preferentially attracted toward DES. The tie lines are then regressed via nonrandom two liquid and universal quasichemical models, which give root mean square deviation (RMSD) in the range of 0.29-0.35% and 0.39-0.75%, respectively. Finally, the quantum-chemical-based conductor-like screening model-segment activity coefficient is used to predict the tie lines, which gives an RMSD of 2.1-5.2%. A hybrid extractive distillation flowsheet is then used for scale up, process economics, and solvent recovery aspects in ASPEN using DES as a "pseudocomponent."
ABSTRACT
In this study liquid phase equilibrium compositions were measured at 298.15 K under atmospheric pressure for (water + propan-1-ol + diethyl carbonate (DEC) + benzene or cyclohexane or heptane) quaternary systems and (water + DEC + propan-1-ol or benzene or cyclohexane) ternary systems. Good correlation of the experimental LLE data was seen for the measured systems by both modified and extended UNIQUAC models. The solubility of DEC in aqueous and organic phases is shown by equilibrium distribution coefficients calculated from the LLE data.
ABSTRACT
The aim of this work was to study the application of a stochastic algorithm to correlate the experimental data of island-type systems in ternary systems. Thermodynamic NRTL and UNIQUAC models were used to evaluate the activity coefficients. Results regarding the application of the stochastic algorithm were in good agreement with those presented in the current literature. However, generalization of the method proposed in the present work remained an intriguing and complex task so as to reach broad conclusions.
ABSTRACT
Se determinó el equilibrio líquido-líquido (ELL) de los sistemas ternarios benceno + (hexano, heptano y ciclohexano) con el líquido iónico 1-etil-3-metilimidazolio etilsulfato (EMIM-EtSO4) a 308,15 K; la selectividad (S) y el coeficiente de distribución (β) se calcularon desde los datos experimentales que se utilizaron para determinar la capacidad del líquido iónico como solvente para la separación del aromático desde sus mezclas con hidrocarburos alifáticos. La región de inmiscibilidad aumentó en el siguiente orden: ciclohexano < hexano < heptano. La consistencia de los datos experimentales del ELL es evaluado usando la ecuación de Othmer-Tobias. La composición de las fases en equilibrio se correlacionó con los modelos para coeficientes de actividad NRTL y Uniquac.
The equilibrium liquid-liquid (ELL) of ternary systems benzene + (hexane, heptane and cyclohexane) with the ionic liquid 1-ethyl-3-methylimidazolium ethylsulfate (EMIM-EtS0(4)) at 308.15 K, selectivity (S) and the distribution coefficient (β) are calculated from experimental data. The ability of ionic liquid as solvent for separation of the aromatic from their mixtures with ali-phatic hydrocarbons is analyzed. The region of immiscibility increased in the following order: cyclohexane < hexane < heptane. The consistency of the experimental data of ELL is evaluated using the equation of Othmer-Tobias. The composition of the phases in equilibrium is correlated with the models for the activity coeffcient NRTL and UNIQUAC.
O equilíbrio líquido-líquido (ELL) de los sistemas ternários benzeno + (hexa-no, heptano e ciclo-hexano) com o líquido iônico 1-etil-3-metilimidazólio etilsulfato (EMIM-EtS0(4)) com 308,15 K, seletividade (S) e o coeficiente de distribuição (β) são calculados a partir dos dados experimentais. Ela determina a capacidade de líquido iônico como solvente para a separação de aromático a partir de suas misturas com hidrocar-bonetos alifáticos. A região de imiscibilidade aumentou na seguinte ordem: ciclo-hexano < hexano < heptano. A consistência dos dados experimentais de ELL é avaliada usando a equação de Othmer-Tobias. A composição das fases de equilíbrio foi correlacionada com os modelos para coeficientes atividade NRTL e Uniquac.