Solubility Measurement and Mathematical Correlation of Ticagrelor in Different Pure Solvents

Abstract

The solid–liquid phase equilibrium of ticagrelor in methanol, ethanol, n-propanol, isopropanol, 1-butanol, isobutanol, n-octanol, acetonitrile, ethyl acetate, toluene, 2-butanone, and cyclohexanone at the temperature range from 273.15 to 313.15 K was measured by using the isothermal dissolution equilibrium method under the pressure of 101.2 kPa. The solubility data were analyzed by high-performance liquid chromatography, and the results increased with the rising temperature. The maximum value was obtained in 2-butanone at 313.15 K (in mole fraction, 7.758 × 10–2), and the lowest was in toluene at 273.15 K (in mole fraction, 3.0 × 10–5). The result from high to low at all researched temperatures obeyed the following sequence: cyclohexanone > 2-butanone > methanol > ethyl acetate > ethanol > 1-butanol > n-propanol > isopropanol > n-octanol > isobutanol > acetonitrile > toluene. The effect of intermolecular force between the solvent and solute on solubility was analyzed. Moreover, the solubility result in different solvents was correlated by the modified Apelblat equation and λh equation. The largest relative average deviation (RAD) value is 2.79% correlated by the λh equation in acetonitrile. Compared with experimental and calculated values along with RAD values, the result of the modified Apelblat equation is slightly better than that of the λh equation.

Solid–Liquid Equilibrium and Thermodynamic Properties of 6-Bromo-2-chloro-8-cyclopentyl-5-methylpyrido[2,3]pyrimidin-7(8H)-one in 10 Pure Solvents and 3 Different Miscible Systems at T = (278.15–323.15) K

“…The reason why 6-bromo-2-chloro-8-cyclopentyl-5-methylpyrido­[2,3]­pyrimidin-7­(8 H )-one is dissolved in THF may be due to THF, and 6-bromo-2-chloro-8-cyclopentyl-5-methylpyrido­[2,3]­pyrimidin-7­(8 H )-one has the same ring structure; moreover, the oxygen atom on the furan ring of THF has a lone pair of electrons, which will form a strong NH···O bond with the NH on the unsaturated ring of 6-bromo-2-chloro-8-cyclopentyl-5-methylpyrido­[2,3]­pyrimidin-7­(8 H )-one to improve solubility. Both 6-bromo-2-chloro-8-cyclopentyl-5-methylpyrido­[2,3]­pyrimidin-7­(8 H )-one and DMF have amide groups, which may be the reason for the dissolution in DMF. Isophorone, ethyl acetate, and the solute have the same carbonyl structure, which may be the reason for the solute dissolution.…”

“…x A is the mole fraction of THF in the binary solvent without the solute, with uncertainty u(x A ) = 0.005. h i b i t e d .of electrons, which will form a strong NH•••O bond with the NH on the unsaturated ring of 6-bromo-2-chloro-8-cyclopentyl-5-methylpyrido[2,3]pyrimidin-7(8H)-one to improve solubility. Both 6-bromo-2-chloro-8-cyclopentyl-5methylpyrido[2,3]pyrimidin-7(8H)-one and DMF have amide groups, which may be the reason14 for the dissolution in DMF. Isophorone, ethyl acetate, and the solute have the same carbonyl structure, which may be the reason for the solute dissolution.…”

Solubility Measurement of Crystal Form II and Form V Ticagrelor in Several Pure Organic Solvents

“…Chen et al have reported the solubility data of TCG in methanol, ethanol, n-propanol, isopropanol, n-butanol, ethyl acetate, 2-butanone, and cyclohexanone. 37 In this work, the solubility data of Form V TCG in the same eight solvents and of Form II TCG in n-propanol, isopropanol, n-butanol, and ethyl acetate have been measured. The comparison charts of solubility data are shown in Figures 14 and 15.…”

Solubility Behavior of l-Arginine α-Ketoglutarate in Ten Pure and Two Binary Water + Ethanol and Water + Acetone Solvent Systems

“…The λ h model (eq ) was proposed by Buchowski et al It is based on the solid–liquid equilibrium relationship, which can relate the solubility to temperature. − It could reveal the relationship between the activity of a solvent under equilibrium conditions and the solubility data of a solute in a hydrogen bonding system. In eq , λ and h are two adjustable parameters, which are related to the associated number of solute molecules and the excess enthalpy of the solution. − T m is the melting temperature (K) of AAKG. …”