摘要
目的:以Invega Sustenna^(®)为参考进行制剂的仿制研究,并进行Invega Sustenna^(®)和自研棕榈酸帕利哌酮缓释注射液的体外表征研究和体内药动学研究。方法:采用激光粒度分析法确定了Invega Sustenna^(®)粒径分布范围,采用湿磨法制备了棕榈酸帕利哌酮缓释注射液;通过体外溶出实验、扫描电镜(SEM)、差示扫描量热(DSC)、粉末X射线衍射(XRPD)和红外光谱(IR)对Invega Sustenna^(®)和自研棕榈酸帕利哌酮缓释注射液进行了体外表征,并进行了大鼠体内的药动学研究。结果:确定了Invega Sustenna^(®)的粒径分布范围为d(0.1)=0.13~0.30μm;d(0.5)=0.60~1.00μm;d(0.9)=2.00~3.00μm;Span=2.0~3.0;自研棕榈酸帕利哌酮缓释注射液与不同批次Invega Sustenna^(®)间溶出曲线的相似因子均大于50;研磨前后棕榈酸帕利哌酮的晶型及结构无显著变化,且自研棕榈酸帕利哌酮缓释注射液和Invega Sustenna^(®)的外部形貌、晶型及结构均保持一致。药动学研究中,自研棕榈酸帕利哌酮缓释注射液在大鼠体内的C_(max)值和AUC0-t值分别是Invega Sustenna^(®)的0.99倍和0.93倍,且自研棕榈酸帕利哌酮缓释注射液和Invega Sustenna^(®)C_(max)与AUC比值的90%置信区间均在80%~125%。结论:该研究的自研棕榈酸帕利哌酮缓释注射液与Invega Sustenna^(®)的体外溶出和体内药动学一致,获取的实验数据将为后期的制剂研究提供指导。
OBJECTIVE Invega Sustenna^(®)was used as the reference for the preparation of paliperidone palmitate sustained-release injection, and characterization in vitro and pharmacokinetics in vivo were investigated.METHODS The particle size and distribution range of Invega Sustenna^(®)were determined by laser particle analysis. Paliperidone palmitate sustained-release injection was prepared by a wet milling method. Invega Sustenna^(®)and test paliperidone palmitate sustained-release injection were characterized by in vitro dissolution experiment, scanning electron microscopy(SEM), differential scanning calorimetry(DSC), X-ray powder diffraction(XRPD) and infrared spectroscopy(IR), and the pharmacokinetics of Invega Sustenna^(®) and test paliperidone palmitate sustained-release injection were studied in rats.RESULTS The particle size and distribution range of Invega Sustenna^(®) were determined as d(0.1)=0.13-0.30 μm, d(0.5)=0.60-1.00 μm, d(0.9)=2.00-3.00 μm, span=2.0-3.0. The similarity factors of dissolution curves between test paliperidone palmitate sustained-release injection and various batches of Invega Sustenna^(®) were all more than 50. There was no significant change in the crystal and structure of paliperidone palmitate before and after milling, and the morphology, crystal and structure of test paliperidone palmitate sustained-release injection and Invega Sustenna^(®) were consistent. In pharmacokinetic study, the C_(max)value and AUC0-tvalue of test paliperidone palmitate sustained-release injection in rats were 0.99 times and 0.93 times of that of Invega Sustenna^(®), respectively. The 90% confidence intervals of C_(max)ratio and AUC ratio of test paliperidone palmitate sustained-release injection to Invega Sustenna^(®) were between 80% and 125%.CONCLUSION In this study, the test paliperidone palmitic sustained-release injection and Invega Sustenna^(®) achieved a preliminary consistency of dissolution in vitro and pharmacokinetics in vivo, and the obtained experimental data provide guidance for th
作者
师军凤
王丹
韩晓璐
王增明
郑爱萍
张慧
向梅先
SHI Jun-feng;WANG Dan;HAN Xiao-lu;WANG Zeng-ming;ZHENG Ai-ping;ZHANG Hui;XIANG Mei-xian(School of Pharmaceutical Sciences,South-Central University for Nationalities,Hubei Wuhan 430074,China;Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)
出处
《中国医院药学杂志》
CAS
北大核心
2022年第23期2481-2487,共7页
Chinese Journal of Hospital Pharmacy
基金
国家自然科学基金面上项目(编号:81573357,82073793)。
关键词
棕榈酸帕利哌酮
缓释注射液
体外表征
药动学研究
paliperidone palmitate
sustained-release injection
characteristics in vitro
pharmacokinetics
