Descriptive Study: In silico and Physicochemical Assessment of the Effectiveness of Hydroxy / Amino Acids as Auxiliary Substances to Improve the Complexation Efficiency of β-cyclodextrin towards Bosentan

The effectiveness of certain hydroxy and amino acids as an auxiliary substance to improve the
complexation efficiency (CE) of β- cyclodextrin (βCD) towards Bosentan (BOS), a poorly soluble
endothelin receptor antagonist, were assessed to enhance its physicochemical performance. The
phase solubility studies conducted in distilled water demonstrated a better choice of L-Arginine (ARG)
as an auxiliary substance to improve CE and association constant (Ks) of βCD. As complementary
evidence, in silico calculations were performed to foresee the stability, possible interactions and
geometry of BOS inside the βCD cavity, optimizing ARG 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.
Thermodynamic studies suggested that inclusion phenomenon was entropy driven, and spontaneous.
Prepared lyophilized complexes gave clear, transparent water solution indicating the complexes
possessing lower sized particles of drug, achieved by inclusion phenomenon. The protein binding
study resulted inclusion phenomenon was responsible for maintaining the unbound drug in plasma,
which resulted in minimization of dose and dose frequency. The performance of ternary complex was
found to be appreciating in overall assessment, indicating better effectiveness of ARG as an auxiliary
substance in improving CE of βCD towards BOS.