盐酸决奈达隆纳米晶体的制备及其质量评价

Preparation and quality evaluation of dronedarone hydrochloride nanocrystals

采用反溶剂重结晶结合高压均质法制备盐酸决奈达隆纳米晶体。考察药物浓度、溶剂-反溶剂比、搅拌速度、重结晶温度、高压均质条件及干燥方式等因素对纳晶形貌和粒度的影响。以溶剂-反溶剂比、药物浓度及搅拌速度为主要考察因素,采用3因素3水平的正交设计得到较优的处方工艺为:药物浓度100 mg/mL、溶剂-反溶剂比1∶15、搅拌速度为1 200 r/min、重结晶温度为4～8℃,表面活性剂为F127,浓度为1 mg/mL,高压均质1.2×108Pa,循环10次,喷雾干燥后得到平均粒径为580 nm的超细粉体。采用X射线衍射、差示扫描量热法、扫描电镜、溶解度及体外溶出实验等对原料药及纳晶性质进行分析表征。结果表明,盐酸决奈达隆纳晶超细粉体化学结构及晶型不变,且溶解度及溶出速率明显提高。

Abstract 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 anddrying method on particle morphology and particle size mum conditions were obtained by orthogonal design with were investigated. After single factor screening, the opti- 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 con- centration 100 mg/mL, stirring speed over 1 200 r/rain, recrystalization temperature at 4-8 ℃, homogenisation 10 cycles at 1.2 ×10^8 Pa with 1 mg/mL F127. The products were characterized by differential scanning calorime- ter （DSC）, powder X-ray diffraction（XRD） and scanning tion rates of the nanocomposite particles and crude drug nanocrystals have the same chemical structure and crystal electron microscope（SEM）. The solubility and dissolu- were also determined. The results indicate that all the form as the crystallline dronedarone, and have a significantly enhanced solubility and dissolution rate.