Computer-aided molecular modeling techniques for predicting the stability of drug–cyclodextrin inclusion complexes in aqueous solutions

Molecular modeling was used to investigate factors influencing complex formation between cyclodextrins and guest molecules and predict their stability through a theoretical model based on the search for a correlation between experimental stability constants (Ks) and some theoretical parameters describing complexation (docking energy, host–guest contact surfaces, intermolecular interaction fields) calculated from complex structures at a minimum conformational energy, obtained through stochastic methods based on molecular dynamic simulations. Naproxen, ibuprofen, ketoprofen and ibuproxam were used as model drug molecules. Multiple Regression Analysis allowed identification of the significant factors for the complex stability. A mathematical model (r=0.897) related log Ks with complex docking energy and lipophilic molecular fields of cyclodextrin and drug.