辛伐他汀泊洛沙姆P123/F127混合胶束的制备及表征

Preparation and characterization of simvastatin poloxamer P123/F127 mixed micelles

目的:制备并评价辛伐他汀泊洛沙姆P123/F127混合胶束(simvastatin poloxamer P123/F127 mixed micelles, SIM-MM)。方法:采用薄膜水化法制备混合胶束,以包封率、载药量和渗漏率为考察指标,结合单因素和星点设计-效应面法设计,筛选影响考察指标的关键因素并进行优化,并加以验证以确定SIM-MM最佳处方及工艺参数;通过差示扫描量热法(differential scanning calorimetry, DSC)、傅里叶红外光谱法(Fourier transform infrared spectrometer, FTIR spectrometer)验证SIM-MM的形成;采用透射电镜、粒径测定、Zeta电位进行表征。结果:确定SIM-MM的最佳处方为:P123质量分数为63.64%,F127-P123为170 mg,水相体积为7.5 mL;透射电镜证明SIM-MM为圆球形,DSC和FTIR实验验证胶束形成。SIM-MM的粒径为(19.2±1.3)nm,分散系数为0.094,Zeta电位为-11.3 mV,包封率及载药量分别为(95.31±0.80)%、(7.37±0.04)%,SIM-MM的临界胶束浓度介于纯F127和P123单一胶束之间。结论:制备出的SIM-MM粒径小并具有一定的缓释能力,可为后续研究辛伐他汀在治疗骨再生的体内研究与临床开发奠定基础。

OBJECTIVE To prepare and evaluate simvastatin poloxamer P123/F127 mixed micelles(SIM-MM).METHODS A thin-film hydration method was employed for preparing mixed micelles.Encapsulation rate, drug loading and leakage rate were used as the inspection parameters, along with single factor and star point design-response surface method design, for screening and optimizing the key factors affecting the inspection parameters.And the optimal prescription and process parameters of SIM-MM were determined;the formation of SIM-MM was verified by differential scanning calorimetry(DSC)and Fourier transform infrared(FTIR)spectrometer;transmission electron microscopy, particle size measurement and Zeta potential for characterizing.RESULTS The optimal prescription for SIM-MM was as follows: P123% 63.64%,F127-P123 170 mg and volume of water phase 7.5 mL.Transmission electron microscopy proved that SIM-MM was spherical, and DSC/FTIR verified the formation of micelles.Particle size of SIM-MM was(19.2±1.3)nm, dispersion coefficient(PDI)0.094 and Zeta potential-11.3 mV.Encapsulation efficiency and drug loading were(95.31±0.80)and(7.37±0.04)% respectively and critical micelle concentration of SIM-MM was between pure F127 and P123 single micelles.CONCLUSION With a small particle size and a certain slow-release capability, the prepared SIM-MM provided rationales for subsequent follow-up studies of simvastatin in the treatment of bone regeneration in vivo and clinical development.