929 © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com Journal of Chromatographic Science, 2020, Vol. 58, No. 10, 929–939 doi: 10.1093/chromsci/bmaa064 Advance Access Publication Date: 5 September 2020 Article Article Failure Mode Critical Effect Analysis and Design of Experiment-Based Robust Chromatographic Method for Simultaneous Estimation Lornoxicam and Eperisone Hydrochloride Pintu Prajapati*, Vipul Radadiya, and Shailesh Shah Department of Quality Assurance, Maliba Pharmacy College, Uka Tarsadia University, Maliba Campus, Bardoli- mahuva road, Tarsadi, Mahuva, Surat-394 350, Gujarat, India *Author to whom correspondence should be addressed. Email: pintu.prajapati@utu.ac.in Received 25 October 2019; Editorial Decision 10 August 2020 Abstract Failure mode critical effect analysis and design of experiment-based high performance thin layer chromatography (HPTLC) method has been developed for simultaneous estimation of lornoxicam (LOC) and eperisone hydrochloride (EPR). Failure modes were identified on the basis of prior knowledge and experimental data with the help of Ishikawa diagram for the development of method. The criticality of failure mode was assessed by giving risk priority number and criticality rank on the basis of preliminary experimental trials. The identified critical failure modes were analyzed for their effect by design of experiment (DoE)-based Plackett–Burman screening design. From 11 critical factors, the volume of methanol and modifier in mobile phase composition were found as critical failure modes. Critical failure mode was further analyzed by DoE based on central composite design for study of their relationship with resolution of both drugs. Quadratic model suggested by design was further used for failure mode risk control and navigation of design space for a resolution of both drugs more than 1.5. Failure mode risk control strategy was set for robust HPTLC method for simultaneous estimation of both drugs in laboratory mixture. Developed and validated HPTLC method was applied for assay of LOC and EPR in their laboratory mixture and assay values were found in good agreement with a spiked amount of drugs. Introduction Lornoxicam (LOC) is chemically (3E)-6-chloro-3-[hydroxyl (pyridin- 2-ylamino) methylene]-2-methyl-2,3-dihydro-4H-thieno-[2,3-e][1,2]- thiazin-4-one-1,1-dioxide (Figure 1A) is a widely prescribed anti- inflammatory drug. Eperisone hydrochloride (EPR) is chemically (2RS)-1-(4-ethylphenyl)-2-methyl-3-piperidin-1-ylpropan-1-one monohydrochloride (Figure 1B) and centrally acting muscle relaxant (1, 2). Central Drugs Standard Control Organization (CDSCO) has approved a combination of LOC and eperisone tablet for the improvement of myotonic conditions caused by neck-shoulder-arm syndrome, scapulohumeral periarthritis and low back pain in adult patients only (3). Quality by design (QbD) is a systematic approach that begins with predefined specifications and more emphasis on process understand- ing and control based on the principle of quality risk management. QbD approach applied to development of analytical method is known as analytical quality by design (aQbD). Quality risk manage- ment is an important tool for managing risk in variation of the results of analytical method throughout life cycle management of analytical method. In international council of harmonisation (ICH) countries, QbD approach based on the development of analytical method is Downloaded from https://academic.oup.com/chromsci/article/58/10/929/5901555 by guest on 10 June 2022