Solubility Determination and Correlation of Warfarin Sodium 2-Propanol Solvate in Pure, Binary, and Ternary Solvent Mixtures

Abstract

The solubility of warfarin sodium isopropanol solvate (WS•IPA), a widely used anticoagulant, was determined at temperatures ranging from 278.15 to 333.15 K in four pure solvents (acetone, ethanol, IPA, and water), five binary solvent mixtures (IPA + acetone, IPA + ethanol, IPA + water, IPA + heptane, and IPA + hexane), and five ternary solvent mixtures (IPA + acetone + heptane, IPA + acetone + hexane, IPA + ethanol + heptane, IPA + ethanol + hexane, and IPA + water + heptane) using the polythermal method. It was demonstrated that the solubility of WS•IPA increases with increasing temperature in the pure solvents and at constant solvent composition in the solvent mixtures. In addition, the solubility of WS•IPA in IPA increases with increasing content of acetone, ethanol, and water, which act as cosolvents, and decreases with increasing content of heptane and hexane, which act as antisolvents. The experimental solubility data of *

Solubility Measurements and Correlation of MBQ-167 in Neat and Binary Solvent Mixtures

“…Isothermal , and polythermal − methods are commonly used to measure the solubility of compounds. While the former involves the determination of the solubility at known (isothermal) temperatures, the latter employs known concentrations to determine the temperatures at which solubility is achieved at a constant heating rate. , In this study, the polythermal method was used to determine the solubility of MBQ-167 (1) in eight neat solvents (acetonitrile, 1-butanol, 2-butanol, ethanol, ethyl acetate, methanol, 1-propanol, and 2-propanol) and two binary solvent mixtures [ethyl acetate (2) + heptane (3) and ethanol (2) + water (3)]. An automated multiple reactor system (Crystal16 from Technobis Crystallization Systems) was employed for this study. − The suspensions were prepared in 2 mL sealed glass vials (Fisher Scientific) at predetermined concentrations.…”

“…The λh model equation (eq ) is also commonly employed to correlate the change in solubility of numerous solutes with temperature. − ,,, The λh model equation employed in this study is expressed as where x 1 represents the mole fraction solubility of MBQ-167, T and T m are the absolute and melting temperature of MBQ-167 in Kelvin (K), and λ and h are parameters that model the nonideal properties of the solution and the excess mixture enthalpy of solution, respectively.…”

“…The λh model equation (eq 3) is also commonly employed to correlate the change in solubility of numerous solutes with temperature. [5][6][7]15,17,19 The λh model equation employed in this study is expressed as…”

“…Thus, the present study focuses on the measurement and correlation of the solubility data for MBQ-167 to understand this physicochemical property. The solubility measurements were performed by employing the polythermal method − in eight pure solvents (acetonitrile, 1-butanol, 2-butanol, ethanol, ethyl acetate, methanol, 1-propanol, and 2-propanol) and two binary mixtures [ethyl acetate (2) + heptane (3) and ethanol (2) + water (3)] in a temperature range between 278.15 and 333.15 K. The majority of the solvents selected are classified by the Food and Drug Administration (FDA) as Class 3 solvents (less toxic and lower risk to human health) with the exception of acetonitrile and methanol, which are Class 2 solvents . The Apelblat and λh model equations were used to correlate the experimental solubility data obtained.…”

Solubility and Solubility Modeling of 1,3,5-Tris(1-phenyl-1H-benzimidazol-2-yl)benzene toward Nanodispersions in Organic Solvents

“…It is worth noting that the TPBi solubilities in isopropanol are significantly different from those in ethanol and 1-butanol. The solubilities in isopropanol are lower by at least an order of magnitude, which have nearly the same trends to solubilities of warfarin sodium 2-propanol, 29 halosulfuron-methyl, 30 and 2-acrylamide-2-methylpropanesul-fonic acid 31 in those alcohols. In the studied temperature range, the solubilities of TPBi in isopropyl, ethanol, and 1butanol changed by factors of 6.2, 2.6, and 1.6, respectively.…”