摘要
目的:制备卡巴他赛固体脂质纳米粒(cabazitaxel solid lipid nanoparticles,KBTS-SLN),并进行处方工艺优化、质量和体外释放规律考察。方法:采用薄膜分散法制备KBTS-SLN,以包封率为评价指标,通过Box-Behnken响应面法优化筛选KBTS-SLN的最佳处方和制备工艺,并将其制成冻干制剂。采用Malvern动态光散射仪、透射电镜(transmission electron microscopy,TEM)、差示扫描量热(differential scanning calorimetry,DSC)对KBTS-SLN的理化性质进行表征,并进行了体外释放规律和初步稳定性考察。结果:优化处方为KBTS 0.017 g、硬脂酸0.200 g、泊洛沙姆1880.270 g、蛋黄卵磷脂0.220 g;优化工艺参数为水浴温度53℃,溶胀时间为68 min,超声功率为338 W。KBTS-SLN外观呈类球型且分布均匀,粒径为(216.05±2.1)nm,多分散系数PDI(0.219±0.03),Zeta电位为(-25.3±0.07)m V,包封率为(87.99±1.21)%;冻干后粒径略有增加,包封率略有降低,PDI和平均电位均变化不大。初步稳定性试验结果表明KBTS-SLN冻干品在4℃低温条件下放置90 d后稳定性良好。DSC结果表明卡巴他赛以非结晶态存在于SLN内。体外释放结果显示KBTS和KBTS-SLN在8 h时释药分别为65%和27%,24 h累积释放分别达到85.25%和60.90%,表明KBTS-SLN相对于原料药,具有明显的缓释效果。结论:优化后的卡巴他赛固体脂质纳米粒稳定性较好,粒径较小,包封率较高,具有明显的缓释作用。
Objective: To manufacture cabazitaxel solid lipid nanoparticles,cabazitaxel solid lipid nanoparticles( KBTS-SLN),optimize the formulation and preparation techniques and study the quality and release rate in vitro. Methods: The optimal formulation and preparation process of KBTS-SLN were optimized by Box-Behnken response surface method and the KBTS-SLN was prepared into lyophilized preparations with encapsulation rate as entrapment efficiency indicator. The physicochemical properties of KBTS-SLN were characterized by Malvern dynamic light scatter,transmission electron microscopy( TEM) and differential scanning calorimetry( DSC),and the release rate in vitro and preliminary stability were studied. Results: The optimized prescription was 0. 017 g cabazitaxel,0. 200 g dosage of stearic acid,0. 270 g emulsifier and 0. 220 g emulsifier. The optimized process for bath temperature was 53 ℃ and the swelling time was 68 min with ultrasonic power being 338 W. KBTS-SLN was spherical in shape and uniform in particle size. The average diameter was( 216. 05 ± 2. 1) nm,polydispersity coefficient of PDI was( 0. 219 ± 0. 03),Zeta potential was(-25. 3 ± 0. 07) m V,and encapsulation efficiency was( 87. 99 ± 1. 21) %. After lyophilization,the diameter increased slightly,the encapsulation efficiency decreased slightly,and the PDI and average potential changed little. The results of preliminary stability test showed that the KBTS-SLN lyophilized products had good stability after being placed at a low temperature of 4 ℃ for 90 days. DSC results indicated that cabazitaxel existed in the SLN in an amorphous state. The results of release in vitro showed that KBTS and KBTS-SLN released by 65% and 27% respectively at 8 h,and the cumulative release reached85. 25% and 60. 90% respectively at 24 h,which indicated that KBTS-SLN had a significant sustained release effect compared with the drug substance. Conclusion: The optimized solid lipid nanoparticles of cabazitaxel have good stability,small particle size,high encapsulation efficiency
作者
陈宇婷
蒋芳
邓盛齐
陶静
罗玉莹
张金霞
CHEN Yu-ting;JIANG Fang;DENG Sheng-qi;TAO Jing;LUO Yu-ying;ZHANG Jin-xia(Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province,Sichuan Industrial Institute of Antibiotics,Chengdu 610052,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2020年第2期199-206,共8页
Chinese Journal of New Drugs
