QBD DRIVEN STABILITY INDICATING RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF NINTEDANIB ESYLATE

SANJAY DINKAR SAWANT; JYOTI BHAGWAN TANGDE

doi:10.22159/ijap.2025v17i2.53110

Authors

SANJAY DINKAR SAWANT Department of Pharmaceutical Chemistry, Sinhgad Technical Education Society’s, Smt. Kashibai Navale College of Pharmacy, Pune, Maharashtra, India
JYOTI BHAGWAN TANGDE Department of Pharmaceutical Chemistry, Sinhgad Technical Education Society’s, Smt. Kashibai Navale College of Pharmacy, Pune, Maharashtra, India

DOI:

https://doi.org/10.22159/ijap.2025v17i2.53110

Keywords:

Degradation, Design expert, Factorial design, ICH guidelines, Nintedanib esylate

Abstract

Objective: The present research work focuses on evaluation of Nintedanib esylate (NTB) with development and validation of Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) method pertaining to quality by design-based force degradation study.

Methods: A two-level, two-factorial design has been used with predetermined design specifications using design expert software. The RP-HPLC method was developed with isocratic mode using a C-18 column at a 392 nm detection wavelength.

Results: The calibration curve was found to be linear with R² = 0.9996. Retention Time (RT) was obtained at 6.14; Limit of Detection (LOD) and Limit of Quantitation (LOQ) were found to be 1.4121 μg/ml and 4.2790 μg/ml, respectively. Relative Standard Deviation (RSD) for intraday precision was 1.799% and for interday precision 1.563% respectively. Degradation studies found out the drug is susceptible to acidic, oxidative, and photolytic conditions, while the drug was found to be stable in thermal and alkaline conditions.

Conclusion: The resulting method holds potential for application in routine analysis of nintedanib esylate in capsule formulation in compliance with International Council for Harmonization (ICH) guidelines.

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References

Parmar Y., Shah D., Yashraj A., Majmudar Y., Patel A., Kanakad P., and Sartanpara U., The Novel Analytical Method Development and Validation for Related Substances of Nintedanib Esylate by Rp-HPLC Method, World J. of Phar. Res., 2021, 10(1). ISSN 2277-7105.

Dudhat K., Patel H., Novel Nanoparticulate Systems for Idiopathic Pulmonary Fibrosis: A Review, Asian J. Pharm Clin. Res., 2020, 13(10), doi:10.22159/ajpcr. 2020.v13i11.39035.

Jinju M, Jingyi H, Zidan C, Jiao S, Renren S, Haixia H, Yameng W, Yu L, Tao L, Baozeng Ren, Solubility measurement and thermodynamic properties of Nintedanib Esylate Hemihydrate in pure solvents, J. of Mol. Liq., 2022, 352.doi.org/10.1016/j.molliq.2022.118624, PMID118624.

Toshihiro S. et al Effect of Nintedanib on non‐small cell lung cancer in a patient with idiopathic pulmonary fibrosis a case report and literature review, Thorac Cancer. 2020 Jun; 11(6): 1720–1723. doi:10.1111/1759-7714.13437.

Bhat D., Rane S., “QbD Approach to Analytical RP¬HPLC Method Development and its Validation”, Int. J Pharm. Pharm. Sci., 2011, (3) 1. ISSN- 0975-1491.

Paolo C., the Effectiveness of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis, Familial Pulmonary Fibrosis and Progressive Fibrosing Interstitial Lung Diseases: A Real-World Study, Biomedicines. 2022, 10(8): 1973. doi:10.3390/biomedicines10081973, PMID 36009520

Ogura T, Inoue Y, Azuma A, Homma S, Kondoh Y, Tanaka K, Ochiai K, Sugiyama Y, Nukiwa T. Real-World Safety and Tolerability of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis: Interim Report of a Post-Marketing Surveillance in Japan. Adv Ther. 2023 Apr; 40(4):1474-1493. doi: 10.1007/s12325-022-02411-y, PMID: 36692681.

Yu LX, Amidon G, Khan MA, Hoag SW, Polli J, Raju GK, Woodcock J. Understanding pharmaceutical quality by design. AAPS J. 2014 Jul; 16(4):771-83. doi: 10.1208/s12248-014-9598-3. Epub 2014 May 23. PMID: 24854893.

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human use, ICH Harmonised Tripartite Guideline Pharmaceutical Development Q8 (R2) Current Step 4 version dated August 2009.

Benedetta P., et al. Quality by Design as a risk-based strategy in pharmaceutical analysis: Development of a liquid chromatography-tandem mass spectrometry method for the determination of nintedanib and its impurities. J. of Chrom. A. 2019, (1611). Doi: 10.1016/j.chroma.2019.460615.PMID 460615.

Ramalingam, P., & Jahnavi, B. QbD Considerations for Analytical Development. Pharmaceutical Quality by Design, Academic Press, 2019. 77–108. doi:10.1016/b978-0-12-815799-2.00005-8.

Thorsten V., Cristiana C., Cyrille C., Ruth F., Timothy G., Nomalie J., Bassam N., Jeremy S., Jason S., Jette W., and Todd R., Analytical Quality by Design, Life Cycle Management, and Method Control, The AAPS Journal 2022 24: 34, doi: 10.1208/s12248-022-00685-2.

Divya B., Ravi P., Hema B., Sai G., Sai S., Viharika N., Development and Validation of RP-HPLC Method for the Determination of Nintedanib in Pharmaceutical Dosage Form, Int. J. Pharm. Sci. Rev. Res., 80 (2), 2023; 50-57. doi: 10.47583/ijpsrr. 2023.v80i02.008, ISSN 0976 – 044X.

Kumar R., Kumar V., Singh R., Warde S., Validated RP-HPLC Method for Determination and Quantification of Nintedanib in Pharmaceutical Formulation, Journal of Adv. in Pharmacology, CR Journals,2020, 1 (1), 38-47.

Jadhav S., Bachhav R., Jadhav V., Stability Indicating RP-HPLC Method Development and Validation for Estimation of Nintedanib Esylate in Bulk and Pharmaceutical Dosage Form, WJPPS,12 (7) 2023, doi:10.20959/wjpps20237-25229ISSN:2278-4357.

Yenda P., Katari N., Satheesh B., Gundla R., Muchakayala K., Rekulapally K., Development, stability-indicating assessment, and evaluation of influential method conditions using a full factorial design for the determination of Nintedanib esylate-related impurities. J Sep Sci. 2023 Jun; 46 (11):2200770. doi: 10.1002/jssc.202200770, PMID: 36976154.

Velagacherla V., Nayak Y., Bhaskar V., Nayak Y., A stability indicating method development and validation of a rapid and sensitive RP-HPLC method for Nintedanib and its application in quantification of nanostructured lipid carriers. F1000Res. 2024, 10; 12:1389. F1000Res, doi:10.12688/f1000research.138786.2. PMID: 38948504.

Dhiman V., Balhara A., Singh S., Tiwari S., Gananadhamu S, Kumar T., Characterization of stress degradation products of Nintedanib by UPLC, UHPLC-Q-TOF/MS/MS and NMR: Evidence of a degradation product with a structure alert for mutagenicity, J of Pharma and Biomed Ana, 2021, 199. doi: 10.1016/j.jpba.2021.114037, PMID 33836462.

Dasari P.., Arava V., Ramadevi B., and Kameswarrao Ch V., "Development and validation of a simple and sensitive stability-indicating RP-HPLC assay method for determination of Nintedanib and stress degradation studies." J Chem Pharm Res. 2015, 78, 774-782. ISSN: 0975-7384.

Kohei T, Kenta F, Kotaro Y, Sumio C, Hitoshi T, Facile and Sensitive HPLC-UV method for determination of Nintedanib in rat plasma, Int. J. of Pharm. and Pharma. Sci, 2018, 10, (6). doi:10.22159/ijpps.2018v10i6.25504, ISSN 0975-1491.

Waghmare, S., & Sumithra, M. QbD Based Development and Validation of RP-HPLC Method for Nintedanib Esylate: Application to Bioanalytical and Stability Study in Plasma. Ana. Chem. Let., 2021. 11(3), 392–408. doi:10.1080/22297928.2021.1930581.

Bhole R., Zambade T., Bonde C., Zambre Y., Identification and Characterization of Degradation Products by Using MSMS Studies for Developed and Validated Stability Indicating HPTLC Method for Estimation of Nintedanib Esylate in Pharmaceutical Dosage Form. Eurasian J. of Ana Chem., 2019, 14(2):60-70. ISSN: 1306-3057.

Bhole R., Chadar K., Zambre Y., &Bonde C., Development and validation of HPTLC method for estimation of dofetilide in pharmaceutical dosage form and determination of its degradation profile by MS-MS method. İstanbul Journal of Pharmacy, 2020, 50(2), 71-78, doi: 10.26650/IstanbulJPharm.2019.0052.

Namjoshi S, Dabbaghi M, Roberts MS, Grice JE, and Mohammed Y. Quality by Design: Development of the Quality Target Product Profile (QTPP) for Semisolid Topical Products. Pharmaceutics. 2020 Mar 23; 12(3):287. doi: 10.3390/pharmaceutics12030287. PMID: 32210126.

Vora R., Shah Y., Investigation of Quality Target Process Parameters (QTPP) And Critical Material Attributes (CMA) of Nanocellulose as A Potential Excipient, Int. J. App. Pharm., 11 (4) 2019, 386-395, doi:10.22159/ijap.2019v11i4.33656.

Waghmare S., and Sumithra M., Full factorial experimental design for development and validation of RP-HPLC method for estimation of Apixaban in Bulk and Pharmaceutical Formulations, J of Seybold Rep, 2020, 15: 3428-42. doi.org/10.22159/ijap.2021v13i5.41786.

Jayagopal B., and Murugesh S., "QbD-mediated RP-UPLC method development invoking an FMEA-based risk assessment to estimate Nintedanib degradation products and their pathways." Arabian J. of Chem, 2020, 13, (9): 7087-7103. doi.org/10.1016/j.arabjc.2020.07.014.

ICH Harmonized Tripartite Guideline; Stability testing: Photo stability testing of new drug substances and products Q1B; International Conference on Harmonization, IFPMA, Geneva, Switzerland; 1996.

ICH Harmonized Tripartite Guideline; Stability Testing of New Drug Substances and New Drug Products Q1A (R2); International conference on Harmonization, IFPMA, Geneva, Switzerland; 2003.

ICH Harmonized Tripartite Guideline; Validation of Analytical Procedures: Text and Methodology, Q2 (R1); International conference on Harmonization, IFPMA, Geneva, Switzerland; 2005.