Box-Behnken设计-效应面法优化吴茱萸碱-羟基乙酸共聚物纳米粒处方及体外释药研究  

Formulation optimization of evodiamine-PLGA nanoparticles by Box-Behnken design-response surface method and in vitro release study

作　　者：魏永鸽[1] 黄贺梅[1] 齐园圃 孙永武[1] 李姝颖 范明松 WEI Yong-ge;HUANG He-mei;QI Yuan-fu;SUN Yong-wu;LI Shu-ying;FAN Ming-song(Zhengzhou Railway Vocational&Technical College,Henan Zhengzhou 450052,China;Technique Center,Shanghai Leiyunshang Pharmaceutical Inc,Shanghai 201401,China)

机构地区：[1]郑州铁路职业技术学院,河南郑州450052 [2]上海雷允上药业有限公司技术中心,上海201401

出　　处：《中国医院药学杂志》2021年第23期2416-2422,共7页Chinese Journal of Hospital Pharmacy

摘　　要：目的:Box-Behnken设计-效应面法优化吴茱萸碱聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]纳米粒处方(吴茱萸碱-PLGA纳米粒),考察体外释药行为。方法:单因素考察PLGA用量,油水体积比,泊洛沙姆188浓度,超声功率和时间等因素的影响,采用Box-Behnken响应面法优化吴茱萸碱-PLGA纳米粒处方。采用甘露醇为冻干保护剂,制备吴茱萸碱-PLGA纳米粒冻干粉末,并考察体外释药情况及释药模型。结果:吴茱萸碱-PLGA纳米粒最佳处方为:PLGA用量为445.1 mg、油水体积比1:5.2、泊洛沙姆188质量分数为1.2%。包封率和粒径分别为(75.73±1.33)%和(173.27±6.86)nm,与模型预测值接近。体外释药符合Higuchi模型:M_(t)/M_(∞)=0.1099t^(1/2)+0.0816,缓释特征明显。结论:Box-Behnken实验设计可用于吴茱萸碱-PLGA纳米粒处方研究,为进一步研究奠定了基础。OBJECTIVE To employthe method of Box-Behnken design-response surface to optimize the formulation ofevodiamine[poly(lactic-co-glycolic acid),PLGA]nanoparticles(evodiamine-PLGA nanoparticles)and examine its in vitro release behavior.METHODS The effects of PLGA dosage,oil-to-water volume ratio,poloxamer 188 concentration,ultrasonic power and time were examined by single factor test.Box-Behnken design-response surface method was utilized for obtaining optimal formulation of evodiamine-PLGA nanoparticles.Mannitol was used as a freeze-dry protective agent for preparing freeze-dried powder of evodiamine-PLGA nanoparticles.The in vitro release behavior and release model were also explored.RESULTS The optimal formulation of evodiamine-PLGA nanoparticles:PLGA dosage was 445.1 mg,oil-water volume ratio 1:5.2 and poloxamer 188 concentration 1.2%.Envelopment efficiency and particle size were(75.73±1.33)%and(173.27±6.86)nm.Both were close to their predicted values.The drug release in vitro was conformed to the Higuchi model:M_(t)/M_(∞)=0.1099t^(1/2)+0.0816 and the process demonstrated obvious sustained-release characteristics.CONCLUSION It is feasible to apply Box-Behnken design-response surface method for formulation optimization of evodiamine-PLGA nanoparticles.It provides rationales for further researches.

关 键 词：吴茱萸碱 聚乳酸-羟基乙酸共聚物纳米粒 缓释特征 

分 类 号：R944.9[医药卫生—药剂学]