氟苯尼考纳米结晶的制备及其药剂学性质的考察

目的增加氟苯尼考(FF)的水溶性,制备氟苯尼考纳米结晶(FF-NC)并对其药剂学性质进行体外评价。方法采用微型化介质研磨法,以西林瓶为研磨室,氧化锆珠子为研磨介质,磁力搅拌器为动力装置制备FF-NC,以粒径和多分散系数(PDI)为指标,正交试验得到的优化处方及工艺参数,进一步放大处方,采用喷雾干燥法固化FF-NC,以差式扫描量热分析,X射线衍射分析,傅里叶红外光谱分析对所得纳米结晶进行表征,并考察其饱和溶解度及体外累积溶出度。结果正交试验最优处方制备得到的FF-NC,其粒径为(189.6±3.44)nm,PDI为(0.192±0.021);等比例放大研磨固化,复溶后FF-NC粒径与喷雾干燥前基本相同;X射线衍射图谱和差式扫描量热分析结果均表明氟苯尼考制备成纳米结晶后呈无定型状态;饱和溶解度试验及体外溶出结果表明制备的FF-NC的饱和溶解度和体外累积溶出度明显高于FF原粉。结论微型化介质研磨法为FF-NC制备工艺的筛选提供了简单有效的途径,为放大化制备提供了依据,制备得到的FF-NC速释、高效,值得进一步研究。

Preparation of florfenicol nanocrystals and investigation of its pharmaceutical properties

Objective To prepare florfenicol nanocrystals (FF-NC) and evaluate its pharmaceutical propertiesin vitro by increasing water solubility of florfenicol (FF). Methods The miniaturized medium grinding methodwas adopted, with the vial as the grinding chamber, the zirconia beads as the grinding medium, and the magneticstirrer as the power device to construct the FF-NC, with the particle size and polydispersity index (PDI) as the index.The optimized formulation and process parameters obtained from the test were further amplified and spray-driedto cure FF-NC (FF-NC). The obtained nanocrystals were characterized by differential scanning calorimetry, X-raydiffraction and Fourier transform infrared spectroscopy. The saturated solubility and cumulative release in vitro wereevaluated. Results The FF-NC prepared by the optimal formulation and process of orthogonal test had a particlesize of (189.6±3.44)nm and a PDI of (0.192±0.021). The particle size of FF-NC after redissolution was basically thesame as that before spray drying. X-ray diffraction pattern and differential scanning calorimetry results showed thatFF was amorphous after being prepared into nanocrystals. The results of in vitro dissolution showed that the preparedFF-NC had significantly higher saturation solubility and cumulative dissolution in vitro than FF. Conclusion Theminiaturization media grinding method provides a simple and effective way for the screening of FF-NC, and provides abasis for the preparation of bulk release. The rapid release and high efficiency of FF-NC obtained from the preparationare worthy of further