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Implementation of DMAIC principle-based analytical quality by design approach to simultaneous estimation of metronidazole and ofloxacin by HPTLC method

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Abstract

A robust HPTLC method has been developed for simultaneous estimation of metronidazole and ofloxacin by enhanced analytical quality by design (AQbD) approach using DoE- and risk-based DMAIC principle. The risk-based DMAIC principle was implemented by identification of potential method risk parameters followed by risk assessment by RPN ranking and filtering method. The DoE-based DMAIC principle was implemented by response surface analysis using DoE-based Box–Behnken design followed by framing of control strategy by navigation of MODR for mitigation of risk. The HPTLC method development was carried using silica gel G60 F254 as stationary phase and acetonitrile: water: formic acid: ammonia (9.5:0.5:0.5:0.3, v/v) as mobile phase keeping saturation time of 10 min. The developed method was found to be validated as per ICH Q2 (R1) guideline. The peak of MET and OFL showed good linearity over the concentration range of 50–250 ng/band and 25–125 ng/band, respectively, with a correlation coefficient of more than 0.995. The % RSD of the precision study was found to be less than 2.0. The %recoveries of both drugs were found to be in the range of 98–102%. The method was found to be robust for small deliberate variations in chromatographic conditions. The developed and validated method was applied for the assay of combined dosage forms of metronidazole and ofloxacin, and results were found in compliance with the label claim. The developed method can be used as an eco-friendly analytical tool for quality control of combined dosage forms of metronidazole and ofloxacin in the pharmaceutical industry.

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Abbreviations

MET:

Metronidazole

OFL:

Ofloxacin

DMAIC:

Define, Measure, Analyse, Improve and Control

AQbD:

Analytical quality by design

DoE:

Design of experiments

RPN:

Risk priority number

MODR:

Method operable design region

HPTLC:

High-performance thin-layer chromatography

RP-HPLC:

Reversed phase high-pressure liquid chromatography,

ICH:

International council for harmonization

IUPAC:

International union for pure and applied chemistry

DNA:

Deoxyribonucleic acid

AR:

Analytical reagent

UV:

Ultraviolet

RSD:

Relative standard deviation

ANOVA:

Analysis of variance

LOD:

Limit of detection

LOQ:

Limit of quantitation

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Acknowledgements

The authors of the manuscript are thankful to the principal, Maliba Pharmacy College and the provost, Uka Tarsadia University for providing the necessary infrastructure and facilities to complete the research work.

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

    Pintu B. Prajapati, Nehal M. Patel & Shailesh A. Shah

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  1. Pintu B. Prajapati
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Prajapati, P.B., Patel, N.M. & Shah, S.A. Implementation of DMAIC principle-based analytical quality by design approach to simultaneous estimation of metronidazole and ofloxacin by HPTLC method. J IRAN CHEM SOC 19, 2915–2928 (2022). https://doi.org/10.1007/s13738-022-02503-0

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