Thermodynamics Research Center / ThermoML | Fluid Phase Equilibria

ABSTRACT

In this work the phase equlibria in binary system: (Drug + solvent) was examined and their physicochemical properties were analyzed. The investigated substances were: synephrine (SYN), isoprenaline hydrochloride (IPR) and metaraminol bitartrate (MET). Solubility of this drugs was determined in three solvents: water, ethanol and 1-octanol. The molecular structure of these drugs is based on a phenthylamine skeleton, therefore all studied pharmaceuticals have an aromatic structure with different amounts of hydroxyl groups located at an aromatic ring. They also have different substituents on the amino group inside the chemical chain. The amino-group confers basic properties of the molecule, whereas the phenolic OH group is weakly acidic. The tested substances belong to the group of adrenergic drugs (adrenomimetics) and stimulate the sympathetic nervous system. Solubilities of three drugs were measured in the temperature range from 270K to 450 K at constant pH. All of studied systems were described as simple eutectic phase diagrams, with complete miscibility at liquid phase and non-miscibility in solid phase. The results are presenting as two phases in equilibrium as a function of temperature. These studies are necessity when the drugs are introducing into the pharmaceutical field. The obtained experimental data were correlated with three equations: Wilson, NRTL and UNIQUAC. Moreover dissociation constants and corresponding pKa values of drugs were obtained with Bates Schwarzenbach method at temperature 298.15 K in the buffer solutions. The DSC (differential scanning microcalorimetry) was used to measure thermal basic properties of pure drugs, that is: the glass-transition temperature, temperature of melting, enthalpy of fusion and the heat capacity at the glass-transition temperature.