Purpose

Paracetamol is a well-known OTC drug, and several combinations are available in the market. The numbers of chromatography methods were published for analysis of combined pharmaceutical dosage form of paracetamol. But every combination needs separate and dedicated chromatography condition for analysis. Hence, a chromatography method was developed for simultaneous estimation of some combined pharmaceutical dosage form of paracetamol using QRM and DoE-based quality by design approach.

Methods

Quality risk management (QRM) was done by method risk parameter identification and assessment. The eleven potentially critical method risk parameters were screened for their main effect on the resolution of peaks by Placket Burman design. Further, three critical method risk parameters were analysed for their effect on the resolution of peaks by Box–Behnken design. Method operable design region (MODR) was navigated for optimisation of chromatography method. The chromatography method was used for simultaneous estimation of six combined dosage forms of paracetamol with different drugs.

Results

After QRM and DoE, mobile phase composition, the volume of acid, and plate activation temperature were found to be critical method parameters and optimised by the navigation of MODR. The optimised method gave results of the assay in agreement with the labelled claim of the dosage form.

Conclusion

The developed method can fulfil a requirement of six different chromatography methods for the analysis of combined dosage forms of paracetamol. Hence, the developed chromatography method is versatile, economical, eco-friendly, and robust (VEER) for the simultaneous analysis of six combined dosage forms of paracetamol.

中文翻译：

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VEER色谱法同时估算扑热息痛多种混合剂型的设计方法实现基于QRM和DoE的质量

目的

扑热息痛是一种著名的非处方药，市场上有几种组合。公开了许多色谱方法用于分析扑热息痛的联合药物剂型。但是每种组合都需要单独的专用色谱条件进行分析。因此，开发了一种色谱方法，用于通过设计方法同时使用QRM和基于DoE的质量同时估算扑热息痛的某些组合药物剂型。

方法

通过方法风险参数识别和评估来完成质量风险管理（QRM）。通过Placket Burman设计筛选了11个潜在的关键方法风险参数对峰分离的主要影响。此外，通过Box–Behnken设计分析了三个关键方法风险参数对峰分离度的影响。导航方法可操作设计区域（MODR）以优化色谱方法。色谱法用于同时估计扑热息痛与不同药物的六种组合剂型。

结果

在QRM和DoE之后，发现流动相组成，酸的量和板活化温度是关键的方法参数，并通过MODR导航进行了优化。优化的方法给出了与标记的剂型要求一致的测定结果。

结论

所开发的方法可以满足对乙酰氨基酚组合剂型分析六种色谱方法的要求。因此，所开发的色谱方法通用，经济，环保且耐用（VEER），可同时分析对乙酰氨基酚的六种组合剂型。