Studying of drug solubility in water and alcohols using drug-ammonium ionic liquid-compounds (original) (raw)

Solubility of pharmaceutical compounds in ionic liquids

Fluid Phase Equilibria, 2013

The solubility of N-acetyl-l-cysteine, coumarin and 4-hydroxycoumarin in alternative solvents was studied in this work. The solid-liquid equilibrium (SLE) measurements have been performed using a dynamic (synthetic) method. Melting points and enthalpies of fusion of the pharmaceutical compounds were acquired using a differential scanning calorimetry (DSC). The solubility of N-acetyl-l-cysteine and 4hydroxycoumarin in trifluoromethanesulfonate ionic liquids was found to be significantly higher than in the studied bis(trifluoromethylsulfonyl)amide ionic liquids while coumarin exhibited the opposite behaviour.

Mutual Solubilities of Ammonium-Based Ionic Liquids with Water and with Water/Methanol Mixture

Procedia Engineering, 2012

Over the last two decades, ionic liquids have gained importance as alternative solvents to conventional VOCs in the field of homogeneous catalysis. This success is not only due to their ability to dissolve a large amount of metal catalysts, but it is also due to their potential to enhance yields of enantiopure products. The art of preparation of a specific enantiomer is a highly desired one and searched for in pharmaceutical industry. This work presents a study on solubility in water and in water/methanol mixture of a set of ILs composed of the bis(trifluoromethylsulfonyl)imide anion and of the N-alkyl-triethyl-ammonium cation (abbrev. [N R,222 ][NTf 2 ]) with the alkyl chain R ranging from 6 to 12 carbons. Mutual solubilities between ILs and water, as well as between ILs and methanol/water mixture were investigated in detail. These solubilities were measured using two well-known and accurate experimental techniques based on a volumetric and a cloud-point methods. Both methods enabled us to measure the Tx diagrams reflecting the mutual solubilities between water (or water/methanol) and selected ILs in the temperature range from 293.15 to 338.15 K. The data were fitted by using the modified Flory-Huggins equation proposed by de Sousa and Rebelo and compared also with the prediction carried out by the Cosmo-RS methodology.

Solubility and Dissolution Thermodynamic Data of Mefenamic Acid Crystals in Different Classes of Organic Solvents

Journal of Chemical & Engineering Data, 2013

Different classes of solvents provide different polarity values, which influence the solubility of pharmaceutical solids. In this article, the solubility of mefenamic acid in different classes of organic solvents, including polar protic, dipolar aprotic, and apolar aprotics at a range of temperatures from (298 to 323) K are reported. It has been found that mefenamic acid shows high solubility in dipolar aprotic solvents (N,N-dimethylacetamide, N,N-dimethylformamide, ethyl acetate, and propanone), moderate solubility in polar protic solvents (ethanol and propan-2-ol), and poor solubility in apolar aprotic solvents (hexane, heptane, and cyclohexane) and water.

Effect of 2-hydroxyethylammonium carboxylate protic ionic liquids on the solubility and cytotoxicity of indomethacin

BMC chemistry, 2024

Recently, there is a particular interest to utilize protic ionic liquids (PILs) in drug solubility. This study is exploring the effect of three protic ionic liquids (PILs) based on 2-hydroxyethylammonium carboxylate [2-hydroxyethylammonium acetate (MEAA), 2-hydroxyethylammonium lactate (MEAL), and 2-hydroxyethylammonium propionate (MEAP)] on the solubility of the very poorly soluble drug in water, indomethacin (IMC). The shake flask method was used to measure the experimental solubility of IMC at the different temperatures range (298.15-313.15) K. The results demonstrate significantly enhancment the solubility of IMC in PILs compared to pure water, with an approximate increase of 200 times. The experimental solubility data have been correlated using the empirical models which showed the performance as the order: Modified Apelblat-Jouyban-Acree > Van't Hoff-Jouyban-Acree > Modified Apelblat equations and also the performance for the Wilson model indicated as the order (absolute relative deviation): 2-hydroxyethylammonium acetate (3.030) > 2-hydroxyethylammonium propionate (3.239) > 2-hydroxyethylammonium lactate (7.665). Then the thermodynamic dissolution properties were obtained by usage of Gibbs and Van't Hoff equations to investigate the thermodynamic behavior of the IMC in the aqueous solution PILs. Eventually, the cytotoxicity of the co-solvents (PILs) under study was evaluated using a standard MTT assay. The results showed that the cell viability percentage increased in the following order: MEAA < MEAP < MEAL. These findings indicated that these PILs had low to moderate toxicity. It is noteworthy that the functional groups of the anions were not the only determinant factor of the cytotoxicity. Other factors encompassing concentration, exposure time, and cell line characteristics also had significant effects.

The a priori design and selection of ionic liquids as solvents for active pharmaceutical ingredients

Chemistry - A European Journal, 2017

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Prodrug ionic liquids: functionalizing neutral active pharmaceutical ingredients to take advantage of the ionic liquid form

MedChemComm, 2013

Chemicals. All chemicals unless otherwise stated were purchased from Sigma-Aldrich Chemical Company (Saint Louis, MO) in reagent grade ≥98% and used without further purification. Deionized water used in the buffer preparation and synthesis was obtained with a specific resistivity of 17.25 MΩ. cm at 25 °C from a commercial deionizer by Culligan (Northbrook, IL). Nuclear Magnetic Resonance Spectroscopy (NMR). 1 H and 13 C NMR spectra were collected utilizing a Bruker (Madison, WI) spectrometer 500 MHz Bruker Avance Spectrometer Bruker/Magnex UltraShield 500 MHz magnet operating at 500 MHz for 1 H and 125 MHz for 13 C spectra, respectively. Thermogravimetrical Analysis (TGA). TGA experiments were performed on a TA Instruments (New Castle, DE) model 2950 Thermogravimetric Analyzer under a stream of nitrogen. Samples between 5 and 10 mg were placed on a platinum pan and were heated from 25 °C to 800 °C with a constant heating rate of 5 °C/min and with a 30 min isotherm at 75 °C to remove any remaining volatiles. Decomposition temperatures (T 5%onset) were reported as the onset temperature with respect to the initial 5 wt% mass loss. Differential Scanning Calorimetry (DSC). Thermal transitions were measured on a Mettler Toledo Star DSC unit (samples 2, 3, 4, 5, 7, 8) (Leicester, UK) or a Mettler Toledo DSC1 Star unit (sample 6) under a stream of nitrogen. Samples (5-10 mg) were placed in closed aluminum pan perforated with a pin-hole. A typical cycle consisted of initially heating the samples from 25 to 110 °C at a heating rate of 5 °C/min, a 5 min isotherm, cooling at a rate of 5 °C/min to-70 °C, and a final 5 min isotherm at-70 °C. Sample 6 (~7.5 mg) was heated between 25-70 °C with a heating rate of 5 °C/min followed by a 15 min isotherm and then cooled with a cooling rate of 5 °C/min to-50 °C followed by a 15 min isotherm at-50 °C. The cycle was repeated twice to ensure consistency of the observed thermal transitions. Single Crystal X-ray Diffraction. Data were collected on a Bruker diffractometer with an Apex II CCD area detector equipped with a low-temperature device, using graphite monochromated Mo-Kα radiation (λ = 0.71073 Å). Data were measured at 173 K (-100 °C) using a strategy of omega scans of 0.5° per frame. Data collection, integration, and absorption corrections were performed using the APEX2 1 software suite from Bruker and SADABS. 2 Structure solution and refinement were conducted using the SHELXTL 3 software package from Bruker. Packing diagrams for the structures were made using Mercury from the Cambridge Crystallographic Data Center. 4 The two structures were solved by direct methods. Non-hydrogen atoms in all structures were located from the difference map and refined anisotropically through least squares refinement against F 2. Hydrogen atoms were placed in calculated positions and allowed to ride on the carrier atom. Hydrogen atoms on methyl groups were refined using a riding rotating model. The X-ray crystallographic information file can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC,

Phase equilibria of didecyldimethylammonium nitrate ionic liquid with water and organic solvents

The Journal of Chemical Thermodynamics, 2007

The phase diagrams for binary mixtures of an ammonium ionic liquid, didecyldimethylammonium nitrate, [DDA][NO 3 ], with: alcohols (propan-1-ol, butan-1-ol, octan-1-ol, and decan-1-ol): hydrocarbons (toluene, propylbenzene, hexane, and hexadecane) and with water were determined in our laboratory. The phase equilibria were measured by a dynamic method from T = 220 K to either the melting point of the ionic liquid, or to the boiling point of the solvent. A simple liquidus curve in a eutectic system was observed for [DDA][NO 3 ] with: alcohols (propan-1-ol, butan-1-ol, and octan-1-ol); aromatic hydrocarbons (toluene and propylbenzene) and with water. (Solid + liquid) equilibria with immiscibility in the liquid phase were detected with the aliphatic hydrocarbons heptane and hexadecane and with decan-1-ol. (Liquid + liquid) equilibria for the system [DDA][NO 3 ] with hexadecane was observed for the whole mole fraction range of the ionic liquid. The observation of the upper critical solution temperature in binary mixtures of ([DDA][NO 3 ] + decan-1-ol, heptane, or hexadecane) was limited by the boiling temperature of the solvent. Characterisation and purity of the compounds were determined by elemental analysis, water content (Fisher method) and differential scanning microcalorimetry (d.s.c.) analysis. The d.s.c. method of analysis was used to determine melting temperatures and enthalpies of fusion. The thermal stability of the ionic liquid was resolved by the thermogravimetric technique-differential thermal analysis (TG-DTA) technique over a wide temperature range from (200 to 780) K. The thermal decomposition temperature of 50% of the sample was greater than 500 K. The (solid + liquid) phase equilibria, curves were correlated by means of different G Ex models utilizing parameters derived from the (solid + liquid) equilibrium. The root-mean-square deviations of the solubility temperatures for all calculated data are dependent upon the particular system and the particular equation used. Comparison of the solubilities of different ammonium salts in alcohols, in hexane, in benzene, and in water are discussed.

Rheological and Thermal Behavior of Choline-based Deep Eutectic Ionic Liquid and its Impact on a Poorly Soluble Drug Model

International journal of drug delivery technology, 2023

Objective: This study was conducted to prepare a deep eutectic ionic liquid based on choline chloride and malonic acid (Maline) in different molar ratios and evaluate the maline properties to designate the best ratio for solubilizing risperidone, a poorly soluble drug model. Method: Malines were prepared using choline chloride and malonic acid in 1:0.8, 1:0.9 and 1:1 molar ratios. The characterization of malines involved pH rating, rheological test and thermal behavior using DSC. In addition to estimating the interactions that occur between the choline chloride and malonic acid to form the malines theoretically using the computational prediction program Mercury and experimentally by 1 H-NMR and FTIR. Results: This study shows that all malines (M1-M3) represents an acidic pH and high viscosity with a non-newtonian behavior (shear thinning property) at low temperature while a Newtonian behavior (shear rate-independent) at high temperatures. In malines (M1-M3) thermograms, the absence of pure compounds melting point peaks with a glass transition temperature at-14 ○ C that confirms the DES property. FTIR and 1 H-NMR results represent a hydrogen bond formation between choline chloride and malonic acid and further between maline and risperidone which is similar to the computational prediction. Maline (M1) with molar ratio of 1:1 had a preferable solubilizing effect on risperidone reaching 20.5 mg/mL, while in (M2) (1:0.9) reaches 13.6 mg/mL, and in (M3) reaches 11.9 mg/mL. Conclusion: Maline (M1) was chosen as the optimum molar ratio to form a deep eutectic ionic liquid that successfully enhances risperidone solubility and boosts its bioavailability.