in silico and Physico-Chemical Assessment of Effectiveness of Hydroxy/Amino Acids as Auxiliary Substances to Improve the Complexation Efficiency of ββ ββ β-Cyclodextrin Towards Bosentan

Abstract

The effectiveness of certain hydroxy and amino acids as an auxiliary substance to improve the complexation efficiency of β-cyclodextrin towards bosentan, a poorly soluble endothelin receptor antagonist, were assessed to enhance its physico-chemical performance. The phase solubility studies conducted in distilled water demonstrated a better choice of L-arginine as an auxiliary substance to improve complexation efficiency and association constant (Ks) of β-cyclodextrin. As a complementary evidence, in silico calculations were performed to foresee the stability, possible interactions and geometry of bosentan monohydrate inside β-cyclodextrin cavity, optimizing L-arginine again as an auxiliary substance. Subsequently, the solution state thermodynamic investigations revealed entropy driven complexation process. The lyophilized complexes were characterized by FTIR, DSC, XRPD and SEM. The performance of ternary complex was found to be appreciating in overall assessment, indicating better effectiveness of L-arginine as an auxiliary substance in improving complexation efficiency of β-cyclodextrin towards bosentan monohydrate.