Enhanced solubility and dissolution of curcumin by a hydrophilic polymer solid dispersion and its insilico molecular modeling studies

摘要

Curcumin (CUR) is highly lipophilic drug that shows degradation at alkaline pH which restricts its oral bioavailability. The aim of the present study was to enhance the oral bioavailability of CUR by increasing its solubility and dissolution rate. Solid dispersions (SDs) of CUR in aqueous and organic solvent using Eudragit EPO (EuD) were prepared by spray drying and rota evaporation technique. The solubility of plain CUR in acidic pH 1.2 is only 0.02% whereas SDs containing EuD have solubilities of 40.29% and 18.78% by spray drying and rota evaporation technique respectively. Physical characterization by SEM, IR, DSC, and XRD studies, revealed the changes in solid state during the formation of dispersion and justified the decreased crystallinity of CUR SDs. Dissolution studies showed that pH values influenced the release profile lower the pH values higher the release speed (pH 1.2). CUR in pH 1.2 showed negligible release even after 120 min (2—5%) whereas, SDs showed 20—45% drug release after 60 min. Further, insilico docking study was carried out followed by molecular dynamic simulations to understand the molecular level binding interactions between drug and polymer. The insilico studies demonstrates the role of van der Waals interactions in binding of CUR to EuD.