Host-guest interaction study of Efavirenz with hydroxypropyl‑β‑cyclodextrin and L‑arginine by computational simulation studies: Preparation and characterization of supramolecular complexes

The present study demonstrates the solubility and dissolution enhancement of Efavirenz (EFV) through preparation of supramolecular inclusion complexes. The supramolecular system comprising of EFV, hydroxypropyl‑β‑cyclodextrin (HP-β-CD) and L‑Arginine was prepared by physical mixing and spray drying methods. The complexes were characterized by powder X-ray diffraction, differential scanning calorimetry, ¹H NMR spectroscopy and FT-IR spectroscopy to study alteration in crystallinity of drug. Intrinsic stability constant values (Kc) and complexation efficiency (CE) of HP-β-CD was substantially enhanced due to addition of L‑Arginine. Improved solubility and dissolution was evidenced in the supramolecular system than binary system of EFV and HP-β-CD. Computational modelling and molecular dynamics study revealed that L‑Arginine increased the stability of the complex by bridging between the EFV and the HP-β-CD. It also confirmed that L‑Arginine was positioned on the outer surface of complex and improved polar surface of inclusion complex resulting in increased solubility of the complex. Thus, supramolecular inclusion complexes of EFV with HP-β-CD and L‑Arginine could contribute as an innovative outcome in formulation development of EFV through solubility and dissolution enhancement.