Solubility and lipophilicity of antiarrhythmic drug Dofetilide in modeling physiological media

• Published in: The Journal of chemical thermodynamics 2021-10, Vol.161, p.106512, Article 106512
• Main Authors: Blokhina, Svetlana V., Sharapova, Angelica V., Ol'khovich, Marina V., Perlovich, German L.
• Format: Article
• Language: English
• Subjects: 1-Octanol/buffer (pH 7.4 and 2.0); Antiarrhythmic drug; Distribution coefficients; Hexane/buffer (pH 7.4 and 2.0); Solubility; Thermodynamics
• ISSN: 0021-9614; 1096-3626
• DOI: 10.1016/j.jct.2021.106512

•The thermophysical behavior of antiarrhythmic Dofetilide was studied.•Drug solubility were measured in buffer solutions (pH 7.4 and 2.0), 1-octanol, hexane.•The distribution coefficients of DFT in two biphasic systems were obtained.•Thermodynamics parameters of transfer for drug were calculated. The thermophysical properties of the antiarrhythmic drug Dofetilide have been studied and it has been established that it represents a mixture of polymorphic modifications. The drug solubility in the following aqueous and organic solvents modeling physiological media has been determined: buffer pH 7.4, buffer pH 2.0, 1-octanol and hexane in the temperature range of 293.15–313.15 K by the shake-flask method. The drug solubility changes from 2.4 10−6 to 12.7 10−3 mol·L-1 depending on the solvent chemical nature and at the temperature 298.15 K decreases in the following order: buffer pH 2.0 > buffer pH 7.4 > 1-octanol > hexane. The distribution coefficients of Dofetilide in two-phase systems of 1-octanol/buffer (pH 7.4 and 2.0) and hexane/buffer (pH 7.4 and 2.0) have been determined within the temperature range of 293.15–313.15 K. In all the studied systems, an increase in the buffer solution acidity from pH 7.4 to pH 2.0 lowers the drug distribution coefficient. The experimental data and the calculated thermodynamic functions of Dofetilide transfer from aqueous phase to organic solvent have been discussed based on the compound protolytic properties.