超临界CO_2抗溶剂法制备布洛芬/EC-PVP缓释复合微粒

Preparation of ibuprofen/EC-PVP sustained-release composite particles by supercritical CO2 anti-solvent technology

采用超临界CO2抗溶剂法制备具有缓释效果的布洛芬/乙基纤维素(EC)-聚乙烯醇吡咯烷酮(PVP)复合微粒。以载药量为主要评价指标,采用正交试验设计优选布洛芬/EC-PVP复合微粒的制备工艺,并对优选的工艺组合进行了包封率、粒径分布、电镜分析、红外光谱(IR)、差示扫描量热法(DSC)以及体外溶出等实验分析。正交试验得到的优选工艺为:结晶温度40℃,结晶压力12 MPa,PVP质量浓度4 mg.mL/1,动态CO2流出速度3.5 L.min?1。此工艺条件下,制备得到的复合微粒的载药量和包封率分别为12.14%和52.21%,平均粒径为27.621μm;IR与DSC分析表明PVP与EC可能发生了络合反应;体外溶出实验表明布洛芬/EC-PVP复合微粒具有良好的缓释效果。实验表明,超临界CO2抗溶剂法可制备具有缓释效果的布洛芬/EC-PVP复合微粒。

Ibuprofen/ethyl-cellulose（EC）-polyvinylpyrrolidone（PVP） sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology.With drug loading as the main evaluation index,orthogonal experimental design was used to optimize the preparation process of EC-PVP/ibuprofen composite particles.The experiments such as encapsulation efficiency,particle size distribution,electron microscope analysis,infrared spectrum（IR）,differential scanning calorimetry（DSC） and in vitro dissolution were used to analyze the optimal process combination.The orthogonal experimental optimization process conditions were set as follows： crystallization temperature 40 ℃,crystallization pressure 12 MPa,PVP concentration 4 mg·mL/1,and CO2 velocity 3.5 L·min-1.Under the optimal conditions,the drug loading and encapsulation efficiency of ibuprofen/EC-PVP composite particles were 12.14% and 52.21%,and the average particle size of the particles was 27.621 μm.IR and DSC analysis showed that PVP might complex with EC.The experiments of in vitro dissolution showed that ibuprofen/EC-PVP composite particles had good sustained-release effect.Experiment results showed that,ibuprofen/EC-PVP sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.