Sibutramine characterization and solubility, a theoretical study

Solubility data from sibutramine (SBA) in a family of alcohols were obtained at different temperatures. Sibutramine was characterized by using thermal analysis and X-ray diffraction technique. Solubility data were obtained by the saturation method. The van’t Hoff equation was used to obtain the theoretical solubility values and the ideal solvent activity coefficient. No polymorphic phenomena were found from the X-ray diffraction analysis, even though this compound is a racemic mixture of (+) and (−) enantiomers. Theoretical calculations showed that the polarisable continuum model was able to reproduce the solubility and stability of sibutramine molecule in gas phase, water and a family of alcohols at B3LYP/6-311++G (d,p) level of theory. Dielectric constant, dipolar moment and solubility in water values as physical parameters were used in those theoretical calculations for explaining that behavior. Experimental and theoretical results were compared and good agreement was obtained. Sibutramine solubility increased from methanol to 1-octanol in theoretical and experimental results.

► Sibutramine was used to control obesity and control other diseased conditions.
► Sibutramine is an interesting molecule for its biological effects and very low solubility.
► There are few reports of sibutramine interactions in vitro, with other drugs or solvents.
► There is a lack of theoreticla studies of sIbutramine in different solvents.
► The present sibutramine study allows to predict the solubility of similar poor solubility drugs.