Multicomponent cyclodextrin system for improvement of solubility and dissolution rate of poorly water soluble drug

Abstract

The purpose of the present study was to investigate the interaction of Cinnarizine (CIN) with Hydroxypropyl-β-Cyclodextrin (HPβCD) in the presence of Hydroxy Acids (HA). Various binary and ternary systems of CIN with HPβCD and HA were prepared by kneading and coevaporation methods. For the ternary systems, HA were tried in three different concentrations. The interaction in solution phase was studied in detail by the phase solubility method, and the solid phase interactions were characterized by Fourier Transform Infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), X-Ray Diffractometry (XRD), Scanning Electron Microscopy (SEM) and Proton Nuclear Magnetic Resonance (1H-NMR). Phase solubility revealed the positive effect of HA on the complexation of CIN with HPβCD. Solid phase characterization confirmed the formation of inclusion complex in the ternary systems. Solubility and dissolution studies illustrated that out of three different concentrations tried, HA were most effective at the 1 M concentration level. Ternary systems were very effective in improving the solubility as well as dissolution profile of CIN than the CIN–HPβCD binary systems. FTIR, 1H-NMR and Molecular docking studies gave some insight at molecular level that actually which part of CIN was interacting with the HPβCD. Molecular docking and free energy calculation even enlighten the role of tartaric acid in increasing solubility of CIN in the ternary system. Keywords: Cinnarizine, Hydroxypropyl-β-cyclodextrin, Hydroxy acid, Ternary system