The investigation of binary and ternary sulfobutylether-β-cyclodextrin inclusion complexes with asiaticoside in solution and in solid state

Abstract

Asiaticoside (AS) is poorly water-soluble compound that can lead to low the bioavailability. The aims of this study were to determine the cyclodextrin (CD) solubilization of AS and characterize binary AS/CD and ternary AS/CD/polymer complexes in solution- and solid-state. Thermal stability of AS through heating process was determined and found that It could withstand by heating through sonication method. Phase-solubility profiles showed that β-cyclodextrin (βCD) exhibited the greatest solubilizing effect but sulfobutylether-βCD (SBEβCD) was selected for further investigations due to its relatively high complexation efficiency (CE) value. The effect of polymers that were poloxamer 407 (P407) and chitosan (CS) on CD solubilization were investigated. It was found that the increment of CE was resulted from the formation of ternary complexes or complex aggregates with confirmed by dynamic light scattering and transmission electron microscopy. Proton nuclear magnetic resonance (1H NMR) data indicated that the cyclohexane moiety of AS was totally inserted into the hydrophobic inner cavity of SBEβCD in the presence or absence of polymer. The molecular modeling study displayed the binding orientation of such complex which correlated to 1H NMR result. The solid state characterized by Fourier transform infra-red, differential scanning calorimetry and powder X-ray diffraction demonstrated the formation of binary AS/SBEβCD and ternary AS/SBEβCD/polymer inclusion complexes. The enhancement of AS dissolution was achieved in both binary and ternary complexes. The permeation study showed that ternary AS/SBEβCD/CS nanoparticles exhibited a promising controlled drug release nanocarrier.