Physicochemical, thermodynamic and analytical studies on binary and ternary inclusion complexes of bosentan with hydroxypropyl-β-cyclodextrin

Abstract

The interactions of poorly aqueous soluble endothelin receptor antagonist bosentan (BOS) with hydroxypropyl-β-cyclodextrin (HPβCD) were assessed in presence and absence of an amino acid l-arginine (ARG), to improve its physicochemical properties. Initially, the phase solubility studies conducted in distilled water followed by thermodynamic investigations demonstrated an AL type of solubility profile and an enthalpy driven exothermic complexation process, respectively, in all cases. The analytical evidences for the formation of lyophilized binary and ternary complexes in solid state were generated and confirmed by differential scanning calorimetry (DSC), Fourier transformation infrared spectroscopy (FTIR), X-ray powder diffractometry (XPRD) and scanning electron microscopy (SEM). The solubility and dissolution of binary and ternary complexes were significantly improved upon complexation as compared to BOS alone, supported by decreased logP values of the complexes. However, the complexation efficiency of ternary system was found to be higher than binary, justifying the addition of ARG as an auxiliary substance to reduce the workable amount of HPβCD during formulation.

Keywords

• Bosentan
• Hydroxypropyl-β-cyclodextrin
• Physicochemical
• Inclusion complex
• Thermodynamic
• Analytical