不同粒径黄体酮的制备及评价  

Preparation and evaluation of progesterone injection with different particle size

作　　者：李莉[1] 李琬晴 李迎[1] 高静[1] 张慧[1] 孙建绪[1] 郑爱萍[1] LI Li LI Wan-qing LI Ying GAO Jing ZHANG Hui SUN Jian-xu ZHENG Ai-ping(State Key Laboratory of Toxicology and Medical Countermeasures, Department ofPharmaceutics, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China School of Preclinical Medicine, Beifing University of Chinese Medicine, Beijing 100029, China)

机构地区：[1]军事医学科学院毒物药物研究所药物制剂研究室抗毒药物与毒理学国家重点实验室,北京100850 [2]北京中医药大学基础医学院,北京100029

出　　处：《国际药学研究杂志》2017年第6期609-615,共7页Journal of International Pharmaceutical Research

基　　金：国家自然科学基金面上项目(81573357);国家"重大新药创制"科技重大专项资助项目(2014ZX09507001003;2014ZX09J14103-01A)

摘　　要：目的比较不同粒径黄体酮注射液的释放速度和生物利用度。方法制备黄体酮纳米级、微米级注射液,通过X线粉末衍射分析(PXRD)和傅里叶变换红外光谱分析(FTIR)对两者进行表征,经透析法比较两制剂和黄体酮原料药的溶出速度。HPLC-MS法测定肌注不同药物后大鼠血浆中药物浓度,计算药代动力学参数,并进行统计学分析。结果 PXRD和FTIR分析中,两制剂晶型结构基本无变化,晶型稳定。黄体酮纳米级、微米级注射液在PBS溶液中释放达到90%时分别需要2和4 h,而原料药释放完全需要近40 h。药代动力学实验中,相比市售黄体酮注射液,黄体酮纳米级、微米级注射液的Cmax分别提高了1.8和1.7倍,AUC0-t分别提高了2.95和1.63倍。两者生物利用度均高于黄体酮注射液。结论黄体酮纳米级、微米级注射液的释放速率显著高于原料药,生物利用度均高于市售注射液。Objective To compare the release rate and bioavailability of progesterone injection with different particle sizes.Methods The preparation of progesterone nano sized injection and micron sized injection were performed by power X-ray diffraction（PXRD）and Fourier trensform infrared spectooscory（FTIR）. The dissolution rate of two preparations and progesterone was compared by dialysis Method. HPLC-MS method was used to determine the progesterone concentration of plasma in rats after intramuscular injection of different preparations,and the main pharmacokinetic parameters were calculated and analyzed statistically. Results Based on the analysis of PXRD and FTIR,there were no crystal structure changes between the two preparations and progesterone. The complete release of progesterone nano sized injection and micron sized injection required 2 and 4 h in the PBS solution,respectively,while the release of progesterone required nearly 40 h. In the pharmacokinetic experiment,compared with progesterone injection,the Cmaxof progesterone nano sized injection and micron sized injection were increased by 1.8 and 1.7 times,respectively;the AUC0-twere increased by 2.95 and 1.63 times,respectively. The bioavailability of both was higher than that of progesterone injection. Conclusion The release rate bioavailability of progesterone nano sized injection and micron sized injection is higher than that of progesterone and progesterone injection. Bioavailability of progesterone nano sized injection is higher than that of progesterone micron sized injection.

关 键 词：黄体酮 纳米晶体 释放速度 药代动力学 

分 类 号：R943[医药卫生—药剂学]