开发一种在速释固定剂量青蒿琥酯/本芴醇片中溶出度测定法。
Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets.
机构信息
Jimma University Laboratory of Drug Quality (JuLaDQ) and School of Pharmacy, Jimma University, PO Box 378, Jimma, Ethiopia.
Drug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
出版信息
Malar J. 2020 Apr 7;19(1):139. doi: 10.1186/s12936-020-03209-5.
BACKGROUND
Dissolution of artemether (ART) and lumefantrine (LUM) active pharmaceutical ingredients (APIs) in fixed dose combination (FDC) ART/LUM tablets is one of the critical quality attributes. Thus, the verification of the release profile of ART and LUM from FDC ART/LUM tablets using a robust and discriminatory dissolution method is crucial. Therefore, the aim of this study was to develop and validate an appropriate dissolution method for quality control of FDC ART/LUM tablets.
METHODS
The dissolution medium was selected based on saturation solubility data and sink conditions. The effect of agitation speed, pH and surfactant concentration on the release of ART and LUM was evaluated by employing a two-level factorial experiment. The resulting final method was validated for linearity, precision, robustness and API stability. In addition, the discriminatory power of the method was evaluated using expired and unexpired FDC ART/LUM products.
RESULTS
A suitable dissolution profile of FDC ART/LUM tablets was obtained in 900 ml HCl (0.025 N, pH 1.6) with 1%Myrj 52 using paddle method at 100 rpm and 37 °C. ART and LUM were analysed using a HPLC method with UV detection at wavelengths of 210 and 335 nm, respectively. The results from the stability study showed that ART and LUM were sufficiently stable in HCl (0.025 N, pH 1.6) with 1%Myrj 52 at 37 °C. The method was linear (r = 0.999) over the concentration range of 6.25-100 μg/ml. The results for precision were within the acceptance limit (%RSD < 2). The percent relative standard deviation (< 2%) and statistically non-significant (p > 0.05) difference in release of ART and LUM observed between deliberately changed dissolution method settings (pH = 1.6 ± 0.2 or agitation speed = 100 ± 2) and optimized dissolution conditions revealed the robustness of the dissolution method. The method was capable to discriminate among different FDC ART/LUM products with different quality.
CONCLUSIONS
The developed dissolution method is robust and discriminatory. It can be used in the quality evaluation of FDC ART/LUM tablets.
背景
青蒿琥酯（ART）和盐酸阿莫地喹（LUM）活性药物成分（APIs）在固定剂量复方（FDC）ART/LUM 片剂中的溶解是关键质量属性之一。因此，使用稳健且具有区分力的溶出度方法验证 FDC ART/LUM 片剂中 ART 和 LUM 的释放特征至关重要。因此，本研究的目的是开发和验证一种适当的溶出度方法，用于 FDC ART/LUM 片剂的质量控制。
方法
根据饱和溶解度数据和溶解条件选择溶解介质。通过采用二水平析因实验评估搅拌速度、pH 值和表面活性剂浓度对 ART 和 LUM 释放的影响。最终方法经过线性、精密度、稳健性和 API 稳定性验证。此外，还使用过期和未过期的 FDC ART/LUM 产品评估了该方法的区分力。
结果
在 900 ml HCl（0.025 N，pH 1.6）中，使用桨法在 100 rpm 和 37°C 下，加入 1%Myrj 52，得到 FDC ART/LUM 片剂合适的溶出度曲线。ART 和 LUM 采用 HPLC 法，UV 检测波长分别为 210nm 和 335nm。稳定性研究结果表明，ART 和 LUM 在 37°C 下，在 HCl（0.025 N，pH 1.6）中加入 1%Myrj 52 时足够稳定。该方法在 6.25-100μg/ml 浓度范围内呈线性（r=0.999）。精密度结果在可接受范围内（%RSD<2）。在故意改变溶出度方法设置（pH=1.6±0.2 或搅拌速度=100±2）和优化溶出条件下，观察到 ART 和 LUM 释放的相对标准偏差（<2%）和统计学上无显著差异（p>0.05），表明该溶出度方法具有稳健性。该方法能够区分不同质量的不同 FDC ART/LUM 产品。
结论
所开发的溶出度方法具有稳健性和区分力。可用于 FDC ART/LUM 片剂的质量评价。
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