Improving the Solubilization and Bioavailability of Arbidol Hydrochloride by the Preparation of Binary and Ternary β-Cyclodextrin Complexes with Poloxamer 188

In the current study, the effect of poloxamer 188 on the complexation efficiency and dissolution of arbidol hydrochloride (ADL), a broad-spectrum antiviral agent, with beta-cyclodextrin (beta-CD) was investigated. Phase solubility studies confirmed a stoichiometry of a 1:1 ratio for both ADL:beta-CD and ADL/beta-CD with a 1% poloxamer 188 system with an AL type of phase solubility curve. The stability constants (K1:1) calculated from the AL type diagram were 550 M-1 and 2134 M-1 for AD:beta-CD and ADL/beta-CD with 1% poloxamer 188, respectively. The binary ADL/beta-CD and ternary ADL/beta-CD with 1% poloxamer 188 complexes were prepared by kneading and a solvent evaporation method and were characterized by aqueous solubility, FTIR, PXRD, DSC and SEM in vitro studies. The solubility (13.1 fold) and release of ADL were markedly improved in kneaded ternary ADL/beta-CD with 1% poloxamer 188 (KDB). The binding affinity of ADL and beta-CD was confirmed by H-1 NMR and 2D ROSEY studies. The ternary complex (KDB) was further subjected for in vivo pharmacokinetic studies in rats and a significant improvement in the bioavailability (2.17 fold) was observed in comparison with pure ADL. Therefore, it can be concluded that the solubilization and bioavailability of ADL can be remarkably increased by ADL/beta-CD complexation in the presence of a third component, poloxamer 188.

Automated summary

The study reveals that poloxamer 188 may enhance the solubility of arbidol hydrochloride/beta-cyclodextrin complexes and significantly improve their bioavailability.