Polythermal Study of Solubility of N-[4-(Difluoromethylthio)phenyl]-2-Aminobenzoic Acid in the System Water-1,2-Propanediol

Abstract

The solubility of N- [4-(difluoromethylthio)phenyl]-2-aminobenzoic acid in the system water3 1,2-propanediol was studied over the entire range of the concentrations of the mixed solvent at 288.153 328.15 K.Anthranilic acid derivatives are commonly used in modern pharmacology. N-[4-(Difluoromethylthio)-pheny]l-2-aminobenzoic acid (Difluorant, hereinafter DF), a nonsteroid antiphlogistic with antipsoriasis activity, is among them.Difluorant is a hydrophobic organic compound, sparingly soluble in water, which makes it difficult to create on its basis water-containing medicines in the form of ointments, foams, and emulsions. Therefore, a study of the DF solubility in nonaqueous solvents, which can homogenize hydrophobic and hydrophilic compounds and their mixtures with water, is one of the main stages of development of highly effective and inexpensive drugs. The most commonly used solvent in soft medicines is 1,2-propanediol (1,2-PD) [1].This study is concerned with the DF solubility in the water31,2-PD system over the entire range of the concentrations of the mixed solvent at 288.153 328.15 K. EXPERIMENTALThe water31,2-PD system was prepared gravimetrically. 1,2-Propanediol was preliminarily treated by double vacuum distillation [2]. The quality of 1,2-PD was checked by the density (r 4 25 = 1032.8 kg m !3 ) and dielectric permittivity (e = 29.0 at 25oC). As second component was used double-distilled water. Prior to use, DF was dried for 2 h at 353 K under a pressure of 2.7 kPa. The quality of the preparation was checked by the melting point (T m = 397 K).The DF solubility was studied by the isothermal method, and the concentration of the saturated solution was determined by the electronic spectroscopy. To do this, excess amount of the substance under study was placed in flasks with ground-glass stoppers, the solvent of the required composition was added, and the mixture was kept at a constant temperature controlled to within + 0.1 K with continuous agitation until the thermodynamic equilibrium was attained. The attainment of the equilibrium was monitored by taking the solution samples and measuring their optical density. The equilibrium was assumed to be attained when the optical density A of a series of successively taken solution samples became constant. Then, the solutions were allowed to settle for 33 4 h at the given temperature, after which they were sampled for the analysis. The saturation time was from 10 to 100 h, depending on the concentration of the nonaqueous component.The optical density A was measured on a Specord M-40 spectrophotometer at l = 310 nm. To do this, 2 ml of the transparent saturated solution was diluted with ethanol so that A of the solutions obtained was within 0.33 0.7. Each value of the solubility is the average of 33 4 measurements. The maximum average error in determining the solubility was 233% at a confidence probability of 0.95. The results obtained are presented in the table.Our results show that the DF solubility varies within a wide range depending on the solvent composition a...

Space filling of permethylated β‐cyclodextrin by volatile hydrophobic and hydrophilic guests in polyethylene glycol

“…In order to calculate the distribution constant К с using the experimentally found values (Equation ), the density of the stationary liquid phase ( ρ L ) needs to be known. Temperature dependence of the PEG‐400 density was obtained from previous work . The density of the mixed stationary phase was calculated based on the X‐ray density of an ideally built Me‐β‐CD crystal, assuming there is no volume change after mixing PEG‐400 with Me‐β‐CD.…”