|本期目录/Table of Contents|

[1]张庆明,徐云燕,夏超.盐酸西那卡塞纳米结晶的制备及体外溶出度研究[J].医学研究与战创伤救治(原医学研究生学报),2021,23(04):372-377.[doi:10.3969/j.issn.1672-271X.2021.04.008]
　ZHANG Qing-ming,XU Yun-yan,XIA Chao.Preparation and dissolution in vitro of cinacalcet hydrochlorde nanocrystals[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2021,23(04):372-377.[doi:10.3969/j.issn.1672-271X.2021.04.008]
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盐酸西那卡塞纳米结晶的制备及体外溶出度研究()
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《医学研究与战创伤救治》（原医学研究生学报）[ISSN:1672-271X/CN:32-1713/R]

卷:
第23卷
期数:
2021年04期
页码:
372-377
栏目:
药学研究
出版日期:
2021-08-10

文章信息/Info

Title:
Preparation and dissolution in vitro of cinacalcet hydrochlorde nanocrystals
作者:
张庆明; 徐云燕; 夏超
作者单位：210002南京，东部战区总医院（原南京军区南京总医院）药剂科（张庆明、徐云燕）； 210009南京，江苏省药物研究所有限公司（夏超）
Author(s):
ZHANG Qing-ming1;  XU Yun-yan1;  XIA Chao2
(1. Department of Pharmacy, General Hospital of Eastern Theater Command, PLA, Nanjing 210002, Jiangsu, China；2.Jiangsu Provincial Institute of Materia Medica, Nanjing 210009, Jiangsu, China)
关键词:
盐酸西那卡塞; 纳米晶体; 响应面法; 溶出度研究
Keywords:
cinacalcet hydrochloride;  nanocrystals;  box-behnken design;  dissolution
分类号:
R96
DOI:
10.3969/j.issn.1672-271X.2021.04.008
文献标志码:
A
摘要:
目的探讨盐酸西那卡塞纳米结晶（CINA-NCs）的制备，并进行体外溶出度研究。方法采用沉淀-超声法制备CINA-NCs。基于单因素法和响应面法（Box-Behnken）设计对制备工艺和处方进行优化，以粒径和多分散指数（PDI）为指标，获得制备的最佳工艺条件。采用冷冻干燥法制备纳米结晶粉体，并用扫描电镜（SEM）、差示扫描量热仪（DSC）和X射线粉末衍射仪（XRPD）对制剂进行表征。最后，通过体外溶出度的研究，评价CINA-NCs胶囊的溶解度和溶出度。结果最优工艺是：CINA浓度108 mg/mL，聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物Soluplus浓度2.7 mg/mL，水相与有机相的比例40∶1，超声时间30 min。最佳工艺条件下制备的CINA纳米结晶的粒径和PDI分别为（244±2）nm和0.168±0.001。对冻干后的纳米结晶进行表征，表明在制备过程中晶体未发生变化。用30％（w/v）微晶纤维素（MCC），8％(w/v）交联羧甲基纤维素钠（CCNa）和2％（w/v）滑石粉制备的CINA-NCs胶囊在pH 1.2盐酸缓冲液、pH 4.5醋酸缓冲液、pH 6.8磷酸盐缓冲液和水四种介质中的体外溶出度均高于市售片剂Sensipar和原料药。结论纳米晶体技术制备的西那卡塞纳米结晶可以提高西那卡塞的溶解度，可改善西那卡塞口服给药的药效。
Abstract:
ObjectiveIn order to improve the solubility and bioavailability of cinacarbose hydrochloride, the preparation and the dissolutionin vitro of cinacarbose hydrochloride nanocrystals (CINA-NCs) were studied.MethodsBased on single factor method and Box-Behnken design, with the particle size and polydispersity index (PDI) as indexes, the optimal production process was achieved.ResultsThe optimal production process was that the concentration of CINA was 108 mg/mL. The concentration of Soluplus was 2.7 mg/mL. The ratio of aqueous phase to organic phase was 40∶1. The time of ultrasonic was 30 min. It was investigated that the particle size and PDI of the NC prepared on the basis of the optimal formulation were (244±2)nm and 0.168±0.001, respectively. Nanocrystals were solidified and characterized. There was no crystalline change during preparation and lyophilization. CINA-NC capsules prepared with 30% (w/v) MCC, 8% (w/v) CCNa and 2% (w/v) talcum powder by orthogonal experimental design presented a enhanced in vitro dissolution rate in four medium which were pH 1.2 hydrochloric acid buffer, pH 4.5 acetic acid buffer, pH 6.8 phosphate buffer saline and water.ConclusionThe solubility of CINA can be improved by nano crystallization of CINA .

参考文献/References:

[1]Terai K, Nara H, Takakura K, et al. Vascular calcification and secondary hyperparathyroidism of severe chronic kidney disease and its relation to serum phosphate and calcium levels[J]. Br J Pharmacol, 2009, 156(8):1267-1278.
[2]皱波涛，胡玉清，尤燕华，等.不同方法治疗血透患者重度继发性甲状旁腺功能亢进对肾性贫血的影响[J].东南国防医药，2019, 21 (2): 141-146.
[3]Stollenwerk BR, Iannazzo S, Akehurst R, et al. A decision-analytic model to assess the cost-effectiveness of etelcalcetide vs. Cinacalcet[J].Pharmacoeconomics, 2018, 36(5):603-612.
[4]Qian Y, Chen G, Wang J, et al. Preparation and evaluation of probucol-phospholipid complex with enhanced bioavailability and no food effect[J]. AAPS PharmSciTech, 2018, 19(8):3599-3608.
[5]杨文涛, 杨磊, 姜伟化,等. 盐酸西那卡塞固体分散体片的制备及溶出度评价[J]. 中国药剂学杂志(网络版), 2014, 12(2):53-61.
[6]Cao M,Xue X, Pei X, et al. Formulation optimization and pharmacokinetics evaluation of oral self-microemulsifying drug delivery system for poorly water soluble drug cinacalcet and no food effect[J]. Drug DevInd Pharm, 2018,44(6):969-981.
[7]刘兰，裴希希，陈国广，等.盐酸西那卡塞纳米乳的制备及体内外评价[J].中国药学杂志, 2018, 53(19): 1667-1675.
[8]Lu S, Yu P, He J,et al.Enhanced dissolution and oral bioavailability of lurasidone hydrochloride nanosuspensions prepared by antisolvent precipitation-ultrasonication method[J]. Rsc ADV, 2016, 6（54）: 49052-49059.
[9]Xue X, Chen G, Xu X, et al. A Combined Utilization of Plasdone-S630 and HPMCAS-HF in Ziprasidone Hydrochloride Solid Dispersion by Hot-Melt Extrusion to Enhance the Oral Bioavailability and No Food Effect[J]. AAPS PharmSciTech, 2019, 20(1): 37.
[10]Li Y, Zhao X, Zu Y, et al. Preparation and characterization of paclitaxel nanosuspension using novel emulsification method by combining high speed homogenizer and high pressure homogenization[J] Int J Pharm,2015, 490(1-2): 324-333.
[11]Verma S, Kumar S, Gokhale R, et al. Physical stability of nanosuspensions: Investigation of the role of stabilizers on Ostwald ripening[J]. Int J Pharm, 2011, 406(1-2):145-152.
[12]刘娇, 唐旭东. 壳聚糖纳米传递系统主动靶向作用改善实体瘤微环境研究进展[J]. 医学研究生学报, 2019, 32(4):423-427.
[13]段靖, 周燕萍, 杨辉,等. 不同粒径地塞米松纳米混悬剂的体外透皮行为比较研究[J]. 东南国防医药, 2019,21(3):273-276
[14]朱庆, 曹燕丽, 徐云燕,等. 酸变性法构建转铁蛋白姜黄素纳米粒及其肿瘤靶向性研究[J]. 东南国防医药, 2019, 21(3):262-266.
[15]Neupane YR, Sabir MD, Ahmad N, et al. Lipid drug conjugate nanoparticle as a novel lipid nanocarrier for the oral delivery of decitabine: ex vivo gut permeation studies[J]. Nanotechnology, 2013, 24(41): 415102.
[16]Ghosh I, Schenck D, Bose S, et al. Optimization of formulation and process parameters for the production of nanosuspension by wet media milling technique: Effect of Vitamin E TPGS and nanocrystal particle size on oral absorption[J]. Eur J Pharm Sci, 2012, 47(4):718-728.

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更新日期/Last Update: 2021-08-10