药学学报, 2019, 54(1): 159-165
引用本文:
王梦迪, 薛英, 冷广意, 许丽晓, 闫静静, 余飞, 杨化新, 刘万卉. 醋酸戈舍瑞林微球的体内外相关性研究[J]. 药学学报, 2019, 54(1): 159-165.
WANG Meng-di, XUE Ying, LENG Guang-yi, XU Li-xiao, YAN Jing-jing, YU Fei, YANG Hua-xin, LIU Wan-hui. In vitro-in vivo correlation of goserelin acetate microspheres[J]. Acta Pharmaceutica Sinica, 2019, 54(1): 159-165.

醋酸戈舍瑞林微球的体内外相关性研究
王梦迪1, 薛英2, 冷广意2, 许丽晓1,2, 闫静静2, 余飞1,2, 杨化新3, 刘万卉1,2
1. 烟台大学药学院, 新型制剂与生物技术药物研究山东省高校协同创新中心、分子药理和药物评价教育部重点实验室, 山东 烟台 264005;
2. 山东绿叶制药有限公司长效和靶向制剂国家重点实验室, 山东 烟台 264670;
3. 中国食品药品检定研究院, 北京 102629
摘要:
本研究的目的是对注射用醋酸戈舍瑞林微球建立体内外相关性(in vitro-in vivo correlation,IVIVC)。制备了3种释放速率不同的注射用醋酸戈舍瑞林微球,并对其物理化学性质进行了表征;采用恒温水浴振荡法测定了3种微球的体外释放度曲线并研究了在该条件下的释放机制;以SD大鼠为动物模型,研究3种微球在体内的药代动力学特性,药代动力学实验方案经山东绿叶制药有限公司动物伦理委员会批准实施;血药浓度-时间曲线经% AUC法处理后得到体内累积释放曲线,并与体外累积释放曲线进行相关性分析。结果表明,本文开发的体外释放度测定方法对不同的醋酸戈舍瑞林微球具有良好的区分能力,醋酸戈舍瑞林微球的体内外相关性良好(r >0.98),并在SD大鼠体内具有良好的预测能力。
关键词:    醋酸戈舍瑞林      微球      体外释放度曲线      药代动力学      体内外相关性      预测能力     
In vitro-in vivo correlation of goserelin acetate microspheres
WANG Meng-di1, XUE Ying2, LENG Guang-yi2, XU Li-xiao1,2, YAN Jing-jing2, YU Fei1,2, YANG Hua-xin3, LIU Wan-hui1,2
1. Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai 264005, China;
2. State Key Laboratory of Long-acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co. Ltd, Yantai 264670, China;
3. National Institutes for Food and Drug Control, Beijing 102629, China
Abstract:
The objective of this paper was to establish a level A in vitro-in vivo correlation (IVIVC) for goserelin acetate extended release microspheres for injection. Three kinds of goserelin acetate microspheres with different release rates were prepared and the critical physicochemical properties, such as drug loading, particle size, glass transition temperature and morphology were characterized. In vitro dissolution test of the prepared goserelin acetate microspheres was performed using sample-and-separate method at 45℃ in 5% (v/v) methanol. The morphology of the microspheres and the molecular weight of poly (lactic-co-glycolic acid) (PLGA) of the prepared goserelin acetate microspheres were investigated to research the release mechanism of microspheres. The plasma concentration of goserelin was detected after intramuscular injection of goserelin acetate microspheres to SD rats, and correlated with the in vitro release profiles after processing by percent AUC method. The pharmacokinetic experimental protocol of goserelin acetate microspheres for injection in SD rats was approved by the Animal Ethics Committee of Shandong Luye Pharmaceutical Co., Ltd. The results indicated that the developed sample and separate method was able to detect differences in the release characteristics of the prepared goserelin acetate microspheres, and the in vitro-in vivo correlation of goserelin acetate microspheres was excellent (r > 0.98) and had good predictive ability in SD rats.
Key words:    goserelin acetate    microsphere    in vitro release profile    pharmacokinetics    in vitro-in vivo correlation    predictive ability   
收稿日期: 2018-09-17
DOI: 10.16438/j.0513-4870.2018-0859
基金项目: 国家重大新药创制科技重大专项(2017ZX09101001).
通讯作者: 刘万卉,Tel:86-535-3946176,E-mail:wanhui@luye.com
Email: wanhui@luye.com
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参考文献:
[1] Hickey T, Kreutzer D, Burgess DJ, et al. Dexamethasone/PLGA microspheres for continuous delivery of an anti-inflammatory drug for implantable medical devices[J]. Biomaterials, 2002, 23:1649-1656.
[2] D'Souza SS, Deluca PP. Development of a dialysis in vitro release method for biodegradable microspheres[J]. AAPS PharmSciTech, 2005, 6:E323-E328.
[3] Andhariya JV, Shen J, Choi S, et al. Development of in vitro-in vivo correlation of parenteral naltrexone loaded polymeric microspheres[J]. J Control Release, 2017, 255:27-35.
[4] Rawat A, Bhardwaj U, Burgess DJ. Comparison of in vitro-in vivo release of Risperdal® Consta® microspheres[J]. Int J Pharm, 2012, 434:115-121.
[5] Shen J, Burgess DJ. Accelerated in-vitro release testing methods for extended-release parenteral dosage forms[J]. J Pharm Pharmacol, 2012, 64:986-996.
[6] Shen J, Choi S, Qu W, et al. In vitro-in vivo correlation of parenteral risperidone polymeric microspheres[J]. J Control Release, 2015, 218:2-12.
[7] Burgess DJ, Crommelin DJ, Hussain AS, et al. Assuring quality and performance of sustained and controlled released parenterals[J]. Eur J Pharm Sci, 2004, 21:679-690.
[8] Zhao YQ, Zhou SH, Liu WJ, et al. Discussion of development and validation of dissolution methods for solid oral dosage forms[J]. Acta Pharm Sin (药学学报), 2018, 53:202-209.
[9] FDA:guidance for industry extended release oral dosage forms:development, evaluation, and application of in vitro/in vivo correlation[EB/OL]. US:Department of Human Health and Human Services, Food and Drug Administration, 1997[2018-08-30]. http://www.fda.gov/cder/guidance/index.htm.
[10] Shen J, Burgess DJ. In vitro-in vivo correlation for complex non-oral drug products:where do we stand?[J]. J Control Release, 2015, 219:644-651.
[11] Suarez-Sharp S, Li M, Duan J, et al. Regulatory experience with in vivo-in vitro, correlations (IVIVC) in new drug applications[J]. AAPS J, 2016, 18:1379-1390.
[12] Roudier B, Davit BM, Beyssac E, et al. In vitro-in vivo correlation's dissolution limits setting[J]. Pharm Res, 2014, 31:2529-2538.
[13] Zolnik BS, Burgess DJ. Evaluation of in vivo-in vitro release of dexamethasone from PLGA microspheres[J]. J Control Release, 2008, 127:137-145.
[14] Zhang S, Han JB, Leng GY, et al. An LC-MS/MS method for the simultaneous determination of goserelin and testosterone in rat plasma for pharmacokinetic and pharmacodynamic studies[J]. J Chromatogr B, 2014, 965:183-189.
[15] D'Souza S, Faraj JA, Giovagnoli S, et al. IVIVC from long acting olanzapine microspheres[J]. Int J Biomater, 2014, 2014:407065.
[16] Chu DF, Fu XQ, Liu WH, et al. Pharmacokinetics and in vitro and in vivo correlation of huperzine A loaded poly (lactic-co-glycolic acid) microspheres in dogs[J]. Int J Pharm, 2006, 325:116-123.
[17] Lai HQ, Hu Y, Li XD. The in vitro dissolution of total composition of the tablet of rhizomes of ligusticum chuanxiong components and in vitro-in vivo correlation by the method of area under the absorbance-wavelength curve[J]. Acta Pharm Sin (药学学报), 2015, 50:788-792.
[18] Trelstar®:depot, clinical pharmacology and biopharmaceutics review for NDA[EB/OL]. US:Department of Human Health and Human Services, Food and Drug Administration, 2000[2018-08-30].https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-715_Trelstar_biopharmr_P1.pdf.
[19] Gao KP, Chen QH. Research of method for accelerated in vitro drug release from poly-ester microsphere injection[J]. Chin J New Drugs (中国新药杂志), 2009, 18:614-617.
[20] Somayaji MR, Das D, Przekwas A. A new level a type IVIVC for the rational design of clinical trials toward regulatory approval of generic polymeric long-acting injectables[J]. Clin Pharmacokinet, 2016, 55:1179-1190.
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