Solubility of Sparingly Soluble Drug Derivatives of Anthranilic Acid

Abstract

This work is a continuation of our systematic study of the solubility of pharmaceuticals (Pharms). All substances here are derivatives of anthranilic acid, and have an anti-inflammatory direction of action (niflumic acid, flufenamic acid, and diclofenac sodium). The basic thermal properties of pure Pharms, i.e., melting and glass-transition temperatures as well as the enthalpy of melting, have been measured with the differential scanning microcalorimetry technique (DSC). Molar volumes have been calculated with the Barton group contribution method. The equilibrium mole fraction solubilities of three pharmaceuticals were measured in a range of temperatures from 285 to 355 K in three important solvents for Pharm investigations: water, ethanol, and 1-octanol using a dynamic method and spectroscopic UV-vis method. The experimental solubility data have been correlated by means of the commonly known G(E) equation: the NRTL, with the assumption that the systems studied here have revealed simple eutectic mixtures. pK(a) precise measurement values have been investigated with the Bates-Schwarzenbach spectrophotometric method.

IUPAC-NIST Solubility Data Series. 102. Solubility of Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Neat Organic Solvents and Organic Solvent Mixtures

“…There have been four experimental studies 86,87,89,173 reporting how the solubility of niflumic acid varied with temperature. Surov et al 86 and Perlovich et al 87 both examined the solubility of niflumic acid in hexane and 1-octanol.…”

“…Surov et al 86 and Perlovich et al 87 both examined the solubility of niflumic acid in hexane and 1-octanol. Doma nska et al 89 measured niflumic acid solubilities in ethanol and 1-octanol using a dynamic method that recorded the temperature at which the last crystals of the solid solute disappeared. Bustamante et al 173 reported niflumic acid solubilities in ethyl ethanoate and ethanol in the temperature range between 283 and 308 K. The internal consistency of the six datasets was assessed by curve-fitting the measured mole-fraction solubility data to Eq.…”

“…There have been three studies 89,191,195 examining the solubility of sodium diclofenac as a function of temperature. Zilnik et al 191 determined the solubility of sodium diclofenac in ethyl ethanoate, propanone and dimethyl sulfoxide at several temperatures between 293 and 313 K. The experimental solidliquid equilibrium data were modeled using expressions based on the Nonrandom Two Liquid (NRTL) and UNIQUAC models.…”

“…The authors found that both solution models provided a reasonably accurate mathematical description of the observed solubility behavior of sodium diclofenac in the three solvents, with average relative deviations between the backcalculated and measured data on the order of 2% or less. Nayak 195 measured the solubility of sodium diclofenac in several natural oils (olive oil, castor oil, sunflower oil, soybean oil, and arachis oil) from 300 to 315 K. Doma nska et al 89 determined the mole fraction solubility of sodium diclofenac in both ethanol and 1-octanol at several temperatures using a dynamic method that recorded the temperature at which the last crystal dissolved. The internal consistency of the latter two datasets was assessed by curve-fitting the measured mole fraction solubility data to the Modified Apelblat model [see Eq.…”

Solubility of pharmaceuticals in water and alcohols

“…These values are necessary to describe the thermodynamic solubility. The solubility is not the ideal solubility but is dependent on the solvent [18]. However, the solubility data of many new drugs are often not available in the literature.…”