Development and Validation of RP-HPLC Method for Simultaneous Estimation of Linagliptin and Metformin HCL In Its Bulk and Tablet Dosage Form Using Quality by Design Approach

Authors

  • Shivam S. Lale  Assistant Professor, MET's Institute of D. Pharmacy, Nashik), Dr. Milind P. Wagh Professor, Pharmaceutics, MVP’s COP, Nashik, Maharashtra, India
  • Milind P. Wagh  Assistant Professor, MET's Institute of D. Pharmacy, Nashik), Dr. Milind P. Wagh Professor, Pharmaceutics, MVP’s COP, Nashik, Maharashtra, India

Keywords:

QbD, Metformin HCl, Linagliptin, Box-Behnken design

Abstract

The present study describes a simple, accurate, precise and cost effective reverse phase High Performance Liquid Chromatographic (RP-HPLC) method for determination of Linagliptin and Metformin HCl in bulk marketed tablet formulation. Optimization was done by response surface methodology, applying a three level Box-Behnken design. Three factors selected were flow rate, column length and methanol concentration in mobile phase. The optimized chromatographic method was validated according to the International Conference on Harmonization (ICH) Q2 (R1) guidelines for linearity, range, accuracy and robustness. The separation was carried out using three columns with different length. Detection was done using UV detector at 250 nm. The developed method employed mobile phase methanol : phosphate buffer (pH 4.6) (75:25), temperature 25?c and flow rate 0.8 ml/min, which was optimized with the help of design expert software. High linearity of the developed method was confirmed over concentration range of 400-600 ?g/mL for Metformin HCl & 1.5-3.5 ?g/mL for Linagliptin with correlation coefficient of 0.9979 & 0.9968. The percentage RSD for precision and accuracy of the method was found to be less than 2%. Peaks were obtained at retention times of 2.6 & 5.6 min. respectively for Metformin HCl & Linagliptin. The proposed method can be successfully used to determine the drug contents of marketed formulation.

References

  1. ICH Q8 (R2), 2009. Pharmaceutical Development, Part I: Pharmaceutical Development., http://www.ich.org/LOB/media//MEDIA4986.pdf.
  2. ICH Q9, 2005. Quality Risk Management, http://www.ich.orghttp://www.ich.org/LOB/media//MEDIA1957.pdf.
  3. ICH Q10, 2008. Pharmaceutical Quality Systems., http://www.ich.org.
  4. ICH Q2 R1, VALIDATION OF ANALYTICAL PROCEDURES: TEXT AND METHODOLOGY, 1994, http://www.ich.org
  5. Indian Pharmacopoeia, 2010, Vol. III, The Indian Pharmacopoeia Commission, Ghaziabad, Appendix 3.1.
  6. Bhatt D. A., Rane S. I., “QbD Approach to Analytical RP-HPLC Method Development and its Validation”, Int J Pharm Pharm Sci 3(1), pp. 179-187.
  7. Mohini Bajaj and Sanju Nanda, “Analytical quality by design (AQbD): new paradigm for analytical method development”, International Journal of Development Research, February, 2015, Vol. 5, Issue, 02, pp. 3589-3599.
  8. Phil Nethercote, Phil Borman, Tony Bennett, QbD for Better Method Validation and Transfer, available at-http://www.pharmamanufacturing.com/articles/2010/060/?Show=all
  9. S. Karmarkar, X. Yang, R. Garber, A. Szajkovics, M. Koberda, “Quality by design (QbD) based development and validation of an HPLC method for amiodarone hydrochloride and its impurities in the drug substance”, Journal of Pharmaceutical and Biomedical Analysis, 100 (2014), pp. 167–174.
  10. B. Santhosha, A. Ravindranath, C. Sundari, “Validated method for the simultaneous estimation of Metformin Hydrochloride and Vildagliptin by RP-HPLC in bulk and the pharmaceutical dosage form”, Int. Res J Pharm. App Sci., 2012; 2(3), pp. 22-28.
  11. Subhakar Nandipati, V. Krishna Reddy, T. Ravindranadh Reddy, “Development and Validation of RP-HPLC method for Simultaneous Determination of Vildagliptin and Metformin in Bulk and Formulation Dosage”, Int. Res J Pharm. App Sci., 2012; 2(3), pp. 44-50
  12. P. G. Shelke, A. P. Dewani, R. L. Bakal, S. N. Vasu, A.S. Tripathi and A.V. Chandewar, “A validated RP-HPLC method for simultaneous determination of metformin HCL and Linagliptin in pharmaceutical formulation”, International Journal of Advances in Pharmaceutical Analysis, Vol. 3 Issue 2 (2013), pp. 37-41.
  13. A Madhusudhan Reddy, Ayesha Siddika, P Surya Bhaskara Rao, P Manasa, J Siddaiah, P Srinivasa Babu, “formulation and evaluation of sustained release matrix tablets of Metformin Hydrhocloride”, Indian Journal of Research in Pharmacy and Biotechnology, Volume 1(2), March-April 2013, pp. 197-200.
  14. Chandrabatla Varaprasad, Md. Asif, K.Ramakrishna, “RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF METFORMIN AND LINAGLIPTIN IN TABLET DOSAGE FORM”, Rasayan J. Chem. Vol. 8, No.4, October – December, 2015, pp. 426 – 432.
  15. S. Shirisha, M. Akiful Haque, D. Sireesha, Vasudha Bakshi, S. Harshini, “Development and Validation of RP-HPLC Method for Simultaneous Estimation of Metformin and Linagliptin in Combined Pharmaceutical Dosage Form”, IJPRUR, Volume 2 (6), 2014, pp. 491-495.
  16. Mrs Sheena Moncy, Miss G. Rohini Reddy, Mr. P. Sunil Kumar Chaitanya, Miss G.Priyanka, Miss E. Hima Bindu, “SIMULTANEOUS DETERMINATION OF METFORMIN HYDROCHLORIDE AND LINAGLIPTIN BY RP-HPLC IN BULK AND PHARMACEUTICAL FORMULATIONS”, IAJPR, Vol 4, Issue 10, 2014, pp. 4047-53.
  17. K. Sravana Kumari, B. Sailaja, “ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR ESTIMATION OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS: A REVIEW”, Int. J. Curr. Res. Chem. Pharma. Sci. 2 (4), 2015, pp. 83- 98.
  18. Jadhav M. L., Tambe S. R., Implementation of QbD Approach to the Analytical Method Development and Validation for the Estimation of Propafenone Hydrochloride in Tablet Dosage Form, Chromatogr. Res. Int. 2013. Available on http://dx.doi.org/10.1155/2013/676501 23.
  19. Ramzia I. El-Bagary, Ehab F. Elkady, Bassam M. Ayoub, “Spectrophotometric Methods for the Determination of Linagliptin in Binary Mixture with Metformin Hydrochloride and Simultaneous Determination of Linagliptin and Metformin Hydrochloride using High Performance Liquid Chromatography”, Int J Biomed Sci vol. 9, no. 1, March, 2013, pp. 41-47.
  20. K. Sujatha, J.V.L.N. Seshagiri Rao, “A NEW RP-HPLC METHOD FOR THE ESTIMATION OF LINAGLIPTIN IN TABLET DOSAGE FORMS”, IAJPR, Vol 3, Issue 10, 2013, pp. 8376-81.
  21. Sujan Banik, Palash Karmakar, Md. Anowar Hossain Miah, “Development and Validation of a UV-Spectrophotometric Method for Determination of Vildagliptin and Linagliptin in Bulk and Pharmaceutical Dosage Forms”, Bangladesh Pharmaceutical Journal 18(2), 2015, pp. 163-168.
  22. Garg L.K., Sait S.S., Krishnamurthy T., Kumar C.P., 2014. Quality by Design (Qbd): A Practical Experimental Design Approach by Blocking and Varying Certain Factors of a Stability-Indicating HPLC Method for Simultaneous Determination of Omeprazole and Ketoprofen. J Liq Chrom Rel Tech, pp. 1-32.
  23. Connors K.A., 1999. A textbook of Pharmaceutical Analysis, 3rd ed., John Wiley and sons, pp. 373-390.
  24. Sethi P.D., 2001. “High Performance Liquid Chromatography”, Quantitative Analysis of Pharmaceutical Formulations, 1st ed., CBS Publishers and Distributors, New Delhi, 2001, pp. 3-11, 116-120.
  25. United States Pharmacopoeia, USP35-NF30, pp. 262-265, 2440-2441, 3959-3960.
  26. Jaiprakash N. Sangshetti, Mrinmayee Deshpande, Zahid Zaheer, Devanand B. Shinde, Rohidas Arote, “Quality by design approach: Regulatory need”, Article in press, Arabian journal of Chemistry.
  27. S. Karmarkar, R. Garber, Y. Genchanok, S. George, X. Yang, and R. Hammond, “Quality by Design (QbD) Based Development of a Stability Indicating HPLC Method for Drug and Impurities”, Journal of Chromatographic Science, Vol. 49, July 2011, pp. 439-46.
  28. www.wikipedia.com, Accessed on 27th Dec. 2015, 4:00 PM.

International Journal of Scientific Research in Chemistry

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Published

2021-10-31

Issue

Volume 6, Issue 5, September-October-2021

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Research Articles

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How to Cite

[1]
Shivam S. Lale, Milind P. Wagh, " Development and Validation of RP-HPLC Method for Simultaneous Estimation of Linagliptin and Metformin HCL In Its Bulk and Tablet Dosage Form Using Quality by Design Approach, International Journal of Scientific Research in Chemistry(IJSRCH), ISSN : 2456-8457, Volume 6, Issue 5, pp.01-24, September-October-2021.