Skip to main content
SpringerLink
Log in

Development of an Innovative Quality by Design (QbD) Based Stability-Indicating HPLC Method and its Validation for Clofazimine from its Bulk and Pharmaceutical Dosage Forms

  • Original
  • Published:
Chromatographia Aims and scope Submit manuscript

Abstract

The present research work discusses the systematic Quality by Design (QbD) enabled development of a simple, rapid, economical, and stability-indicating high-performance liquid chromatography (HPLC) method for effective analysis of clofazimine (CFZ). An Ishikawa fish-bone diagram was constructed for initial risk assessment. Analytical target profile (ATP) was defined and critical analytical attributes (CAAs) were assigned to meet these ATP requirements. Taguchi design was applied for screening critical material attributes (CMAs) and critical process parameters (CPPs) making an impact on the assigned CAAs. The major contributing factors were finely tuned using 33 Box-Behnken design with numerical and graphical optimization. Further, the method was validated as per the ICH guidelines and force degradation studies were carried out under different stress conditions. The optimum chromatographic separation was accomplished using 75:25% v/v ratio of methanol and ammonium acetate buffer (0.01 mol/L) as the mobile phase at flow rate 1.0 mL/min, and UV detection at 284 nm. The developed HPLC method was found highly sensitive, specific with linearity ranging between 2 and 10 µg/mL, and correlation coefficient (R2) 0.9995. It showed high accuracy with % recovery between 99.68 and 100.44%. It depicted detection limit and quantitation limit of 0.0066 µg/mL and 0.0199 µg/mL, respectively. In force degradation studies the drug was found to be highly susceptible in alkaline stress conditions. The results reveal successful applicability of the method for the estimation of CFZ from its marketed formulation which can be wisely extrapolated to assess the CFZ from its other formulation systems and different biological samples.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Barry VC, Belton JG, Conalty ML, Denneny JM, Edward DW, O’sullivan JF, Twomey D, Winder F (1957) A new series of phenazines (Rimino-Compounds) with high antituberculosis activity. Nature 179:1013–1015

    Article  CAS  PubMed  Google Scholar 

  2. O’Donnell MR, Padayatchi N, Metcalfe JZ (2016) Elucidating the role of clofazimine for the treatment of tuberculosis. Int J Tuberc Lung Dis 20:S52–S57. https://doi.org/10.5588/ijtld.16.0073

    Article  Google Scholar 

  3. Patil TS, Deshpande AS, Deshpande S (2018) Critical review on the analytical methods for the estimation of clofazimine in bulk, biological fluids and pharmaceutical formulations. Crit Rev Anal Chem 48:492–502

    Article  CAS  PubMed  Google Scholar 

  4. Van Deun A, Maug AKJ, Salim MAH, Das PK, Sarker MR, Daru P, Rieder HL (2010) Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med 182:684–692. https://doi.org/10.1164/rccm.201001-0077OC

    Article  PubMed  Google Scholar 

  5. Global tuberculosis report 2016 World Health Organization (2016) Geneva. (WHO/HTM/TB/2016.13) http://apps.who.int/medicinedocs/en/d/Js23098en/.Accessed 10 Aug 2018

  6. Hwang TJ, Dotsenko S, Jafarov A, Weyer K, Falzon D, Lunte K, Nunn P, Jaramillo E, Keshavjee S, Wares DF (2014) Safety and availability of clofazimine in the treatment of multidrug and extensively drug-resistant tuberculosis: analysis of published guidance and meta-analysis of cohort studies. BMJ Open 4:e004143. https://doi.org/10.1136/bmjopen-2013-004143

    Article  PubMed  PubMed Central  Google Scholar 

  7. Schmidt AH, Molnár I (2013) Using an innovative Quality-by-Design approach for development of a stability indicating UHPLC method for ebastine in the API and pharmaceutical formulations. J Pharm Biomed Anal 78:65–74. https://doi.org/10.1016/j.jpba.2013.01.032

    Article  PubMed  Google Scholar 

  8. Kurmi M, Kumar S, Singh B, Singh S (2014) Implementation of design of experiments for optimization of forced degradation conditions and development of a stability-indicating method for furosemide. J Pharm Biomed Anal 96:135–143. https://doi.org/10.1016/j.jpba.2014.03.035

    Article  CAS  PubMed  Google Scholar 

  9. Yadav NK, Raghuvanshi A, Sharma G, Beg S, Katare OP, Nanda S (2015) QbD-based development and validation of a stability-indicating HPLC method for estimating ketoprofen in bulk drug and proniosomal vesicular system. J Chromatogr Sci 54:377–389. https://doi.org/10.1093/chromsci/bmv151

    Article  PubMed  Google Scholar 

  10. Sandhu PS, Beg S, Katare OP, Singh B (2016) QbD-driven development and validation of a HPLC method for estimation of tamoxifen citrate with improved performance. J Chromatogr Sci 54:1373–1384. https://doi.org/10.1093/chromsci/bmw090

    Article  CAS  PubMed  Google Scholar 

  11. Garg LK, Reddy VS, Sait SS, Krishnamurthy T, Vali ST, Reddy AM (2013) Quality by design: design of experiments approach prior to the validation of a stability-indicating HPLC method for montelukast. Chromatographia 76:1697–1706

    Article  CAS  Google Scholar 

  12. Wingert NR, Ellwanger JB, Bueno LM, Gobetti C, Garcia CV, Steppe M, Schapoval EE (2018) Application of Quality by Design to optimize a stability-indicating LC method for the determination of ticagrelor and its impurities. Eur J Pharm Sci 118:208–215. https://doi.org/10.1016/j.ejps.2018.03.029

    Article  CAS  PubMed  Google Scholar 

  13. Sharma T, Khurana RK, Jain A, Katare OP, Singh B (2018) Development of a validated liquid chromatographic method for quantification of sorafenib tosylate in the presence of stress-induced degradation products and in biological matrix employing analytical quality by design approach. Biomed Chromatogr 32:e4169. https://doi.org/10.1002/bmc.4169

    Article  CAS  PubMed  Google Scholar 

  14. Khedekar G, Mirgane S (2017) Development and validation of stability indicating HPLC assay method for Clofazimine capsules. IPP 5:112–120

    CAS  Google Scholar 

  15. Patel HA, Patel KG, Pathak DS, Patel DJ, Meshram DB (2017) Development and validation of stability indicating RP-HPLC method for estimation of clofazimine in soft gelatine capsule. Int J Pharm Qual Assur 8:32–38

    Google Scholar 

  16. International Conference on Harmonization (ICH) (2005) ICH Harmonised tripartite guideline: Validation of analytical procedures: text and methodology Q2 (R1)

  17. International conference on harmonization (ICH) (1996) Guidance for industry: Q1B photostability testing of new drug substances and products

  18. Singh S, Junwal M, Modhe G, Tiwari H, Kurmi M, Parashar N, Sidduri P (2013) Forced degradation studies to assess the stability of drugs and products. Trends Analyt Chem 49:71–88. https://doi.org/10.1016/j.trac.2013.05.006

    Article  CAS  Google Scholar 

  19. Dong MW (2006) Modern HPLC for practicing scientists. Wiley, New Jersey

    Book  Google Scholar 

Download references

Acknowledgements

Authors are grateful to Chancellor, NMIMS (Deemed-to-be University) and management of SVKM’s NMIMS, School of Pharmacy and Technology Management, Shirpur for providing various reprographic sources for implementing this work.

Author information

Authors and Affiliations

  1. School of Pharmacy & Technology Management, SVKM’s NMIMS, Shirpur, Maharashtra, India

    Tulshidas S. Patil & Ashwini S. Deshpande

Authors
  1. Tulshidas S. Patil
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ashwini S. Deshpande
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ashwini S. Deshpande.

Ethics declarations

Conflict of interest

Authors declare no conflict of interest.

Ethical standards

The present work is in compliance with ethical standards.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Suppl. Figure 1

Ishikawa fish-bone diagram depicting the possible risk factors for the development of HPLC method (PPTX 71 KB)

Suppl. Figure 2 (a-b)

Chromatograms of CFZ standard solution with different solvents (Organic modifiers) (a) acetonitrile and (b) Methanol (PPTX 225 KB)

Suppl. Figure 3

Overlay plot depicting the optimized conditions of the analytical method (PPTX 143 KB)

Suppl. Figure 4 (a-b)

Chromatograms of CFZ from (a) standard solution and (b) sample extracted from marketed soft gelatin capsule (PPTX 141 KB)

Supplementary material 1 (DOCX 18 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patil, T.S., Deshpande, A.S. Development of an Innovative Quality by Design (QbD) Based Stability-Indicating HPLC Method and its Validation for Clofazimine from its Bulk and Pharmaceutical Dosage Forms. Chromatographia 82, 579–590 (2019). https://doi.org/10.1007/s10337-018-3660-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10337-018-3660-8

Keywords

Search

Navigation