Host–Guest Interactions of Risperidone with Natural and Modified Cyclodextrins: Phase Solubility, Thermodynamics and Molecular Modeling Studies

摘要: The solubility of risperidone (Risp) in aqueous buffered cyclodextrin (CD) solution was investigated for α-, β-, γ- and HP-β-CD. effects pH, ionic strength temperature on complex stability were also explored. Neutral Risp tends to form higher order complexes (1:2) with both β- HP-β-CD, but only 1:1 type γ-CD. tendency cyclodextrins is the β-CD > HP-β-CD γ-CD α-CD. formation constant Risp/HP-β-CD increases increasing an opposite trend inherent (S0) Risp, thus indicating significant hydrophobic effect. effect contributes extent 72% towards neutral stability, while specific interactions contribute 4.7 kJ/mol. Thermodynamic studies showed that driven by a favorable enthalpy change (ΔH0=−31.2 kJ/mol, ΔS0=−7 J/mol.K) 1:2 largely entropy changes (ΔH0=−5.0 ΔS0=42 J/mol.K). Complex found vary Risp. Molecular mechanical computations using MM (atomic charges bond dipole algorithms) Amber force fields, which carried out explore possible sites between CDs rationalize stoichiometry, produced similar results concerning optimal inclusion geometries stoichiometries.