Preparation of apixaban-cyclodextrin - D-α-tocopheryl polyethylene glycol 1000 succinate supramolecular inclusion complex: Mechanistic and physicochemical assessment

Apixaban (APX) is a poorly water-insoluble anticoagulant drug. To enhance the solubility and dissolution profile, the APX inclusion complex was prepared using beta cyclodextrin (βCD), methyl beta cyclodextrin (M βCD), and D-ɑ-tocopheryl polyethylene glycol succinate (TPGS). APX complexes were prepared and evaluated for molecular docking, infrared, differential scanning calorimetry, x-ray diffraction, flow property, saturation solubility, and dissolution study. The phase solubility study results displayed the higher stability constant values (Ks, 1:1) for APX: M βCD (817 M -1 ) and APX: M βCD: TPGS (1979 M -1 ) than the APX: βCD (651 M -1 ) and APX: M βCD: TPGS (1463 M -1 ). The computational docking between the APX and the target protein factor Xa inhibitor exhibited a docking score of -8.58 Kcal/mol. The receptors βCD (-6.77 Kcal/mol) and M βCD (-7.97 Kcal/mol) also displayed high docking scores. The ternary complex (F5, F6) displayed enhanced solubility and dissolution compared to the binary complex (F2, F3). The solid-state characterization confirms the formation of an amorphous complex after the inclusion of APX in cyclodextrin. From the findings, it can be concluded that the addition of water-soluble carriers to develop an inclusion complex could be a new way to enhance the solubility and dissolution profile of APX, which may also promote permeability as well as bioavailability.