Background Numerous chromatographic methods have been published for estimation of fixed-dose combinations (FDCs) of aspirin and ramipril with other drugs. But no published report has been found which promotes simultaneous estimation of FDCs of aspirin and ramipril with other drugs using a single chromatography condition. Objective Hence, the HPTLC method was developed for simultaneous estimation of FDCs of aspirin and ramipril with the drugs under study to save solvent, cost, and time for analysis using a risk- and DoE-based AQbD approach. Method The risk-based AQbD approach was implemented using the risk priority number (RPN) ranking and filtering method as per the ICH Q9 guideline. The DoE-based AQbD approach was applied through a screening study using Placket-Burman design, followed by response surface analysis by Box-Behnken design as per the ICH Q8 guideline. Results The risks from critical method risk parameters were mitigated by navigating method operable design ranges and framing the control strategy for the target method. The method was validated as per ICH Q2 (R1) guidelines. The developed method was applied for simultaneous assay of six different FDCs of aspirin and ramipril and results agreed with the label claims. Conclusions The developed method is the best alternative to published chromatographic methods for estimation of the FDC products under study and saves solvent, time, and cost of analysis. Hence, the developed “GERV”-chromatography method is found to be green (G), economical (E), robust (R), and versatile (V), for estimation of the said FDC products. Highlights Development of GERV-chromatography for simultaneous estimation of multiple FDCs of ramipril and aspirin using a risk-based AQbD approach. Application of the developed method for simultaneous estimation of six different FDC products.

中文翻译：

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使用 DoE 和基于风险的设计方法提高分析质量的 GERV 色谱法估计雷米普利和阿司匹林的多种固定剂量组合产品

背景 已经发表了许多用于估计阿司匹林和雷米普利与其他药物的固定剂量组合 (FDC) 的色谱方法。但尚未发现促进使用单一色谱条件同时估计阿司匹林和雷米普利与其他药物的 FDC 的已发表报告。目的 因此，开发了 HPTLC 方法，用于同时估计阿司匹林和雷米普利与所研究药物的 FDC，以节省溶剂、成本和使用基于风险和 DoE 的 AQbD 方法进行分析的时间。方法 根据 ICH Q9 指南，使用风险优先级数 (RPN) 排名和过滤方法实施基于风险的 AQbD 方法。通过使用 Placket-Burman 设计的筛选研究应用了基于 DoE 的 AQbD 方法，然后按照 ICH Q8 指南通过 Box-Behnken 设计进行响应面分析。结果通过导航方法可操作设计范围并为目标方法制定控制策略，减轻了关键方法风险参数的风险。该方法根据 ICH Q2 (R1) 指南进行了验证。所开发的方法用于同时测定阿司匹林和雷米普利的六种不同 FDC，结果与标签声明一致。结论 所开发的方法是已发表的色谱方法的最佳替代方法，用于估计研究中的 FDC 产品，并节省了溶剂、时间和分析成本。因此，发现开发的“GERV”色谱方法是绿色 (G)、经济 (E)、稳健 (R) 和通用 (V) 的方法，用于评估所述 FDC 产品。强调使用基于风险的 AQbD 方法同时估计雷米普利和阿司匹林的多个 FDC 的 GERV 色谱的发展。应用所开发的方法同时估计六种不同的 FDC 产品。