Preparation, characterization and in vitro cytotoxicity study of dronedarone hydrochloride inclusion complexes

Abstract Dronedarone is a new antiarrhythmic drug for the treatment of atrial fibrillation. This study investigated the complexation of dronedarone hydrochloride with β‑cyclodextrin (β-CD) and 2‑hydroxypropil‑β‑CD (HP-β-CD) using three different techniques. The complexes in the solid state were characterized by DSC, TGA, PXRD, FT-IR, SEM and 1 H NMR, demonstrating the formation of the inclusion complexes and exhibiting different properties from the pure drug. Its aqueous solubility increased about 4.0-fold upon complexation with β-CD and HP-β-CD. The dissolution rate of the drug was notably improved in all tested physiological pH values from 1.2 to 6.8 in the presence of both cyclodextrins. Furthermore, an in vitro cytotoxic assay revealed that the inclusion complexes could reduce the cytotoxic effects of the drug on 3T3 cells. The overall results suggest that the inclusion complexes with β-CD and HP-β-CD may be potentially useful in the preparation of novel pharmaceutical formulations containing dronedarone hydrochloride.