Development and Validation of A HPLC-UV Method for Dissolution Testing of Ciclosporin: Its Application to The Measurement of Brand and Generic Versions from Different Countries

Badr Aljohani, F. FaisalAlotaibi, E. Ghazaly, J. Jaber, D. Perrett, A. Johnston
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引用次数: 5

Abstract

Ciclosporin is used as an immunosuppressant in post-organ transplantation. Recently, many questions have been raised about using generic substitutes, especially with narrow therapeutic index drugs (NTIDs). In this study, a simple high-performance liquid chromatography (HPLC) method was developed, validated and applied to detection ciclosporin in dissolution testing. Seven ciclosporin products (gelatin capsules) were included in this study, obtained from Columbia (C), Egypt (E), India (I), Jordan (J), Pakistan (P), Saudi Arabia (S), and Turkey (T). The dissolution test was done for all capsules. The Conditions were as follows: 500 ml deionized water as the medium in apparatus 2 (Pharmatest, Germany), temperature 37.5 ± 0.5°C; 50 rev/min, sampling times were 5, 10, 15, 30, 60 and 90 min with 5 ml for each sample. HPLC separation was done by a C18 column, 5 μm, (4.6 × 250 mm, ACE 5) held at 50 ± 0.3°C. Analytes were isocratically eluted at 0.7 ml/min with acetonitrile and water (70+30%) and 0.03% trifluoroacetic acid, over the 25-min run time. The intra-day and inter-day imprecision for ciclosporin across the standard range was <5% and <4%, respectively. The accuracy of the assay was within ± 13% of the true value at standard curve concentrations range from 0.1 to 2 mg/ml of ciclosporin. The lower and the upper limit of detection were 0.001 mg/ ml and 2 mg/ml of ciclosporin, respectively. All brands (S, T, P, J, E) and one generic (C) showed more than 80% of ciclosporin after 90 min (90.3, 100, 90.4, 82.7, 81.4 and 90.6%) respectively. One generic (I), showed less than the minimum percentage of labeled amount, 69.1%. Relative to the brand (T), statistical analysis showed significant differences (P<0.0001) of the mean percentage content between brand and generic. The 95% confidence interval range for the brands (E, J, P, and S) was (72.2-91.8), (73.4-93.3), (80.2-101.9), and (80.1-101.8), respectively, and (80.3-102.1), and (61.3-77.9) for the generic (C) and (I) respectively. Based on these results, we conclude that some of the ciclosporin preparations do not contain the exact mass labeled and the majority contained as yet unidentified impurities.
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HPLC-UV环孢素溶出度测定方法的建立与验证:在不同国家品牌和仿制药溶出度测定中的应用
环孢素被用作器官移植后的免疫抑制剂。近年来,关于使用非专利替代品,特别是窄治疗指数药物(NTIDs),提出了许多问题。本研究建立了一种简便的高效液相色谱(HPLC)检测环孢素溶出度的方法。选取哥伦比亚(C)、埃及(E)、印度(I)、约旦(J)、巴基斯坦(P)、沙特阿拉伯(S)和土耳其(T)的7种环孢素产品(明胶胶囊)作为研究对象,对所有胶囊进行溶出度测定。实验条件为:以500ml去离子水为介质,在2号仪器(德国Pharmatest)中,温度37.5±0.5℃;50转/分钟,取样时间分别为5、10、15、30、60和90分钟,每种样品5ml。HPLC分离采用C18色谱柱,5 μm, (4.6 × 250 mm, ACE 5),温度为50±0.3°C。用乙腈和水(70+30%)和0.03%三氟乙酸以0.7 ml/min的等压洗脱分析物,运行时间为25 min。环孢素在标准范围内的日内和日内不精确度分别<5%和<4%。在环孢素浓度为0.1 ~ 2mg /ml的标准曲线范围内,测定的准确度在真实值的±13%以内。环孢素的检出下限为0.001 mg/ml,上限为2 mg/ml。所有品牌(S、T、P、J、E)和1个仿制药(C)在90 min后环孢素含量均超过80%(分别为90.3、100、90.4、82.7、81.4和90.6%)。1个仿制药(I)低于最低标示量百分比69.1%。相对于品牌(T),统计分析显示品牌和仿制药的平均百分比含量差异显著(P<0.0001)。品牌(E, J, P, S)的95%置信区间分别为(72.2-91.8),(73.4-93.3),(80.2-101.9)和(80.1-101.8),仿制药(C)和(I)的95%置信区间分别为(80.3-102.1)和(61.3-77.9)。根据这些结果,我们得出结论,一些环孢素制剂不含有确切的质量标记,大多数含有尚未鉴定的杂质。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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