基于 DOE 的分析失效模式关键影响分析 (AFMCEA) 应用于多用途反相高效液相色谱法，采用分析质量源于设计方法评估盐酸二甲双胍的多种复方制剂产品。

DoE-Based Analytical Failure Modes Critical Effect Analysis (AFMCEA) to a Multipurpose-RP-HPLC Method for the Estimation of Multiple FDC Products of Metformin Hydrochloride Using an Analytical Quality by Design Approach.

机构信息

Department of Quality Assurance, Maliba Pharmacy College, Uka Tarsadia University, Bardoli-Mahuva Road, Tarsadi, Mahuva, Surat 394 350, Gujarat, India.

出版信息

J AOAC Int. 2022 Jun 29;105(4):986-998. doi: 10.1093/jaoacint/qsac025.

DOI:10.1093/jaoacint/qsac025

PMID:35176154

Abstract

BACKGROUND

Metformin hydrochloride is the first-choice antihyperglycemic agent and its several fixed-dose combinations (FDCs) with pioglitazone hydrochloride, sitagliptin phosphate, and gliclazide are used for the management of type II diabetes. Numerous reversed-phase HPLC (RP-HPLC) and HPTLC methods have been reported for estimation of FDCs of metformin but each FDC needs separate and dedicated chromatographic conditions for analysis. No RP-HPLC method has been reported yet which promotes synchronous estimation of FDC products of metformin to save time, resources, cost, and organic solvent for analysis.

OBJECTIVE

Hence, an economical and eco-friendly RP-HPLC method was developed for the synchronous estimation of FDCs of metformin hydrochloride using an enhanced analytical quality by design (AQbD) approach.

METHODS

The AQbD approach was implemented using analytical-failure modes critical effects analysis (FMCEA) as per International council for harmonisation (ICH) Q8 and Q9 guidelines. The analytical-FMCEA was applied by identification of potential analytical failure modes followed by their risk assessment by a risk priority number (RPN) ranking and filtering method. Further, the risk of critical failure modes was controlled and mitigated by a design of experiments (DoE)-based Box-Behnken design by navigation of method operable design ranges (MODR).

RESULTS

From the set of control strategies, the RP-HPLC method was developed using a Shim-Pack ODS C18 column and acetonitrile-0.1% triethylamine (40:60, v/v) triethylamine in water (pH 3.2 adjusted by perchloric acid). The method was found to be validated as per ICH Q2 (R1) guideline. The synchronous estimation of different FDCs of metformin hydrochloride was carried out by the developed method.

CONCLUSION

The developed method can be used as a multipurpose chromatography method as an alternative to published chromatography methods for QC of FDCs of metformin hydrochloride in the pharmaceutical industry.

HIGHLIGHTS

The multipurpose RP-HPLC method has been developed and validated for the synchronous estimation of multiple combined pharmaceutical dosage forms of metformin hydrochloride. The method was developed by the implementation of the AFMCEA-based AQbD approach as per the regulatory requirements of ICH.

摘要

背景

盐酸二甲双胍是治疗糖尿病的一线药物，其与盐酸吡格列酮、磷酸西他列汀和格列齐特的几种固定剂量组合（FDC）也被用于 2 型糖尿病的治疗。已经有许多反相高效液相色谱（RP-HPLC）和高效薄层色谱（HPTLC）方法被报道用于评估 FDC 中的盐酸二甲双胍，但每种 FDC 都需要单独和专用的色谱条件进行分析。还没有报道过可以同时评估盐酸二甲双胍 FDC 产品的 RP-HPLC 方法，这种方法可以节省分析时间、资源、成本和有机溶剂。

目的

因此，开发了一种经济且环保的 RP-HPLC 方法，用于通过增强分析设计（AQbD）方法同步评估盐酸二甲双胍的 FDC。

方法

根据国际人用药品注册技术协调会（ICH）Q8 和 Q9 指南，使用分析失效模式关键影响分析（FMCEA）实施 AQbD 方法。通过识别潜在的分析失效模式，应用分析-FMCEA，然后通过风险优先数（RPN）排序和筛选方法对其进行风险评估。进一步通过基于实验设计（DoE）的 Box-Behnken 设计，在可操作设计范围（MODR）内导航，控制和减轻关键失效模式的风险。