title: Computer Simulation Studies of the Mechanism of Hydrotrope-Assisted Solubilization of a Sparingly Soluble Drug Molecule.
abstract: The effect of hydrotrope sodium cumene sulfonate (SCS) on the solubility of a sparingly water-soluble drug, griseofulvin, is studied by employing classical molecular dynamics simulation technique. We mainly focus on the underlying mechanism by which SCS enhances the solubility of a sparingly soluble or insoluble solute in water. The main observations are the following: (a) The self-aggregation of SCS molecules (through its hydrophobic tail) above the minimum hydrotrope concentration (MHC) causes the formation of micellar-like frameworks. Interestingly, though the drug griseofulvin possesses both polar and nonpolar groups, it prefers to get encapsulated inside the hydrophobic core of SCS aggregates. The decomposition of total SCS-drug interaction energy into van der Waals and electrostatic components suggests that the former plays a major role in this interaction. (b) The calculated Flory-Huggins interaction parameter values give a strong indication of the mixing ability of hydrotrope SCS and griseofulvin drug molecules. (c) As expected, we do not observe any strong effect of SCS aggregates on SCS-water and water-water average hydrogen-bond number, but it affects water-drug griseofulvin average hydrogen-bond number. With the help of these observations we try to elucidate the hydrotropic action of hydrotrope SCS on the solubility of drug griseofulvin.
authors.affiliation: Department of Chemistry, Indian Institute of Technology , Guwahati, Assam 781039, India.
authors.forename: Shubhadip
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Chemistry, Indian Institute of Technology , Guwahati, Assam 781039, India.
authors.forename: Sandip
authors.initials: S
authors.lastname: Paul
mesh_terms: D001555:Benzene Derivatives / Q000737:chemistry; D006118:Griseofulvin / Q000737:chemistry*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D001555:Benzene Derivatives; D014867:Water; D006118:Griseofulvin; C015763:cumene