Preparation and quality evaluation of dronedarone hydrochloride nanocrystals

Dronedarone hydrochloride nanocrystals were prepared by antisolvent recrystallization combined with subsequent homogenization.The effects of the solvent to antisolvent volume ratio,drug concentration,stirring speed, recrystalization temperature,homogenization condition (pressure,circle numbers),type of surfactants and drying method on particle morphology and particle size were investigated.After single factor screening,the optimum conditions were obtained by orthogonal design with 3 factors and 3 levels according to the antisolvent volume ratio,drug concentration and stirring speed.The results indicated that nanocrystals with average 580 nm particle diameter were obtained from the slurry when the ratio of methanol to the hydrochloric acid was 1 ∶15,drug concentration 100 mg/mL,stirring speed over 1 200 r/min,recrystalization temperature at 4-8 °C,homogenisation 10 cycles at 1.2×10⁸ Pa with 1 mg/mL F127.The products were characterized by differential scanning calorimeter (DSC),powder X-ray diffraction(XRD) and scanning electron microscope(SEM).The solubility and dissolution rates of the nanocomposite particles and crude drug were also determined.The results indicate that all the nanocrystals have the same chemical structure and crystal form as the crystallline dronedarone,and have a significantly enhanced solubility and dissolution rate.