Page 33 - 2019年9月第30卷第17期

国内3厂家环孢素软胶囊的体外溶出评价研究 Δ

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孙 婷 ，姜建国 ，张 菁 ，张西如 ，徐艳梅 ，王 柳（1.河北省药品检验研究院非标研究室，石家庄
1＊
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050011；2.河北省药品检验研究院质保室，石家庄 050011；3.河北省药品检验研究院化妆品室，石家庄
050011；4.河北省药品检验研究院化学室，石家庄 050011）
中图分类号 R927.1；979.5 文献标志码 A 文章编号 1001-0408（2019）17-2332-05
DOI 10.6039/j.issn.1001-0408.2019.17.06

摘 要 目的：考察国内环孢素软胶囊仿制药与参比制剂（原研药）在6种溶出介质中体外溶出曲线的相似性。方法：采用桨法进
行溶出度试验，以含2％十二烷基硫酸钠（SDS）的pH 1.2盐酸溶液、含2％SDS的水溶液、含2％SDS的pH 4.5醋酸盐缓冲溶液、含
2％SDS的pH 5.5 醋酸盐缓冲溶液、含2％SDS的pH 6.8磷酸盐缓冲溶液和含2％SDS的模拟胃液为溶出介质，转速为50 r/min；采
用高效液相色谱法测定环孢素的含量，色谱柱为Agilent Eclipse XDB-C18，流动相为乙腈-水-磷酸溶液（73∶27∶0.25，V/V/V），流速为
1.0 mL/min，检测波长为226 nm，柱温为60 ℃，进样量为20 μL；通过绘制6种介质下的溶出曲线，并采用相似因子（f2 ）法考察国内
3厂家样品（共5批）与1批原研药的相似性。结果：环孢素检测质量浓度线性范围为5～250 μg/mL（r＝0.999 6～0.999 9）；方法学
考察中精密度、稳定性（12 h）、重复性试验的 RSD均＜2.0％（n＝6或7），回收率为98.4％～99.7％（RSD均小于2.0％，n＝9）；在含
2％ SDS的pH 1.2盐酸溶液以及含2％SDS的模拟胃液这2种介质中，6批样品15 min的累积溶出量均达到85％；5批仿制药与原
研药溶出曲线的 f2在含2％SDS的水溶液中分别为75、45、57、42、83，在含2％SDS的pH 4.5醋酸盐缓冲溶液中分别为44、76、38、
32、76，在含2％SDS的pH 5.5 醋酸盐缓冲溶液中分别为76、47、49、40、79，在含2％SDS的pH 6.8磷酸盐缓冲溶液中分别为52、49、
55、48、80。结论：3个国内厂家5批环孢素软胶囊仿制制剂与原研药在体外溶出曲线相似性方面比较显示有差异。
关键词 环孢素软胶囊；相似性；体外溶出；仿制药；原研药

Study on Dissolution in vitro of Cyclosporine Soft Capsules from 3 Domestic Manufacturers
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SUN Ting ，JIANG Jianguo ，ZHANG Jing ，ZHANG Xiru ，XU Yanmei ，WANG Liu （1.Dept. of Quality
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Consistency Evaluation，Hebei Institute for Drug Control，Shijiazhuang 050011，China；2.Dept. of Director of
Quality Management，Hebei Institute for Drug Control，Shijiazhuang 050011，China；3.Dept. of Cosmetics，
Hebei Institute for Drug Control，Shijiazhuang 050011，China；4.Dept. of Chemical，Hebei Institute for Drug
Control，Shijiazhuang 050011，China）
ABSTRACT OBJECTIVE：To investigate the similarity of in vitro dissolution curve between the generic drugs and the reference
preparation（original drugs）of the domestic Cyclosporine soft capsules in 6 dissolution mediums. METHODS：The dissolution test
was performed with paddle method. 2％ SDS water solution，2％ SDS pH 1.2 hydrochloric acid solution，2％ SDS water solution，
2％ SDS pH 4.5 acetate buffer solution，2％ SDS pH 5.5 acetate buffer solution，2％ SDS pH 6.8 phosphate buffer solution and
2％ SDS simulated gastric fluid were used as the dissolution medium，and the rotation speed was 50 r /min. HPLC method was
used. The determination was performed on Agilent Eclipse XDB-C18 column with mobile phase consisted of acetonitrile phosphate
solution（73 ∶ 27 ∶ 0.25，V/V/V），the flow rate was 1.0 mL/min. The detection wavelength was set at 226 nm，the column temperature
was 60 ℃，and sample size was 20 μL. The dissolution curves in 6 medium were drawn and the similarity factor（f2 ）was used to
investigate the similarity between the samples from 3 domestic manufacturers（5 batches）and a batch of original drugs. RESULTS：
The linear range of cyclosporine was 5-250 μg/mL（r＝0.999 6-0.999 9）；RSDs of precision，stability（12 h）and reproducibility
tests were lower than 2.0％（n＝6 or 7）；the recoveries were 98.4％-99.7％（RSD＜2.0％，n＝9）. The cumulative dissolution of 6
batches of samples within 15 min reached 85％ in 2％ SDS pH 1.2 hydrochloric acid solution and 2％ SDS simulated gastric juice.
f2 of the dissolution curve of 5 batches of generic and original drugs of Cyclosporine soft capsules were 75，45，57，42，83 in 2％
SDS water solution and 44，76，38，32，76 in 2％ SDS pH 4.5 acetate buffer solution 76，47，49，40，79 in 2％ SDS pH 5.5
acetate buffer solution and 52，49，55，48，80 in 2％ SDS pH 6.8 phosphate buffer solution，respectively. CONCLUSIONS：
There have differences in the similarity of the dissolution
Δ 基金项目：国家科技重大专项-重大新药创制（No.2017zx0910-
curve between the domestic generic and the original drugs of 5
1001）
batches of Cyclosporin soft capsule from 3 domestic
＊高级工程师。研究方向：药物分析。电话：0311-85212009-
manufacturers.
80378。E-mail：122547652@qq.com
# 通信作者：主任药师。研究方向：化学药物的质量标准。电话： KEYWORDS Cyclosporine soft capsules； Similarity；
0311-85212009-8037。E-mail：1343777894@qq.com Dissolution in vitro；Generic drugs；Original drugs

·2332 · China Pharmacy 2019 Vol. 30 No. 17 中国药房 2019年第30卷第17期