ABSTRACT:
The applicability of a quality by design (QbD) approach for the development of a sensitive and selective stability indicating reversed-phase high performance liquid chromatography (RP-HPLC) method for the estimation of Ivabradine and Metoprolol was investigated. Design of experiments using a fractional factorial design approach was used for method development. Fifteen experimental runs were performed to optimize the chromatographic conditions like mobile phase, flow rate and column oven temperature. Mobile phase composition was optimized by changing Acetonitrile composition ranging between 13 and 17% v/v, Flow rate from 0.6 to 1.0 ml/min and temperature between 30 to 50 0C. The optimized method produced sharp peaks with good resolution (>2) for Metoprolol and Ivabradine with retention times of 3.3 and 9.2 min, respectively. The experimental data revealed that volume of Acetonitrile in mobile phase was prominently affecting the Retention time, Resolution & tailing factor of both the drugs. Normal probability plots revealed that the residual and predicted data fall approximately on a straight line, indicating that the experimental error for these studies was evenly distributed suggesting that the model could be used to navigate the design space. This approach is useful to expedite method development and optimization activities in analytical laboratories.
Cite this article:
Noopur K. Gandhi, Sindhu B. Ezhava. Stability indicating Analytical Method Development using Quality by Design (QbD) approach for simultaneous estimation of Ivabradine and Metoprolol. Research Journal of Pharmacy and Technology. 2021; 14(11):5937-4. doi: 10.52711/0974-360X.2021.01032
Cite(Electronic):
Noopur K. Gandhi, Sindhu B. Ezhava. Stability indicating Analytical Method Development using Quality by Design (QbD) approach for simultaneous estimation of Ivabradine and Metoprolol. Research Journal of Pharmacy and Technology. 2021; 14(11):5937-4. doi: 10.52711/0974-360X.2021.01032 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2021-14-11-58
REFERENCE:
1. Du XJ, Feng X, Gao XM, Tan TP, et al. If channel inhibitor Ivabradine lowers heart rate in mice. British J. of Pharmacology. 2004; 142: 107-112.
2. Heusch G. Pleiotropic action(s) of the bradycardic agent ivabradine cardiovascular protection beyond heart rate reduction. British J. Of Pharmacology. 2008.
3. Tardi CJ, Ford I, Tendera M, et al. Efficacy of Ivabradine, a new selective If inhibitor, compared with atenolol in patients with chronic stable angina. European Heart J. 2005; 26: 2529-2536.
4. Evans ND, Godfrey KR, Chapman MJ, et al. An Identifiability Analysis of a Parent–Metabolite Pharmacokinetic Model for Ivabradine. J. Pharmacokinetics and Pharmacodynamics. 2001; 28: 93.
5. Ivabradine, C27H36N2O5–PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/Ivabradine, [Accessed 1.09.20]
6. Indian Pharmacopoeia, Government of India Ministry of Health and Family Welfare, The Indian Pharmacopoeia Commission, Ghaziabad. 2018, 2583-2593.
7. United State pharmacopoeia and National formulary, Asian Edition, USP 40 NF 35, The United State Pharmacopeial Convention Rockville. 2017, 5135-5146.
8. Maryadele, N. J. The Merck Index an Encyclopedia of chemicals drugs and biological,12th ed. Merck Research Laboratories, UK, 2006, 6234.
9. Ptaszynski P, Kaczmarek K, Ruta J, et al. Ivabradine in combination with Metoprolol succinate in the treatment of inappropriate sinus tachycardia. J. Cardiovasc. Pharm. T. 2013; 18(4): 338-344.
10. Zarifis J, Kallistratos M and Katsivas A. Antianginal Efficacy of Ivabradine and Metoprolol Combination in Patients with Stable Angina. Clin. Cardiol. 2016; 39(12): 697-702.
11. Patil P, Raj H, Sonara G. Simultaneous Estimation of Atenolol and Ivabradine HCl using UV- Spectrophotometry. Asian J. Pharm. Ana. 2016; 6(2): 109-114.
12. Mohite M, Dudhabale V, Chandgude K. Validation of Stability Indicating RP-HPLC, Method of Analysis for assay of Ivabradine HCl in SR Tablet. Asian J. Pharm. Ana. 2019; 9(3):133-137.
13. Patil P, Raj H, Sonara G. Q-Absorbance Ratio Spectrophotometric method for simultaneous determination of Atenolol and Ivabradine HCl in synthetic mixture. Asian J. Res. Pharm. Sci. 2016; 6(1):27-33.
14. Thete P, Saudagar R. Analytical Method Development and Validation for the Determination of Ivabradine HCl by RP-HPLC in bulk and Pharmaceutical Dosage form. Asian J. Pharm. Tech. 2019; 9(2):89-92.
15. Rajanit S, Virani P, Raj H. Absorption Correction Method for Simultaneous Estimation of Nifedipine and Metoprolol Succinate in Their Synthetic Mixture Using from Spectrophotometry. Asian J. Pharm. Tech. 2015; 5(1): 13-16.
16. Phale M, Hamrapurkar P. A Validated and Simplified RP-HPLC of Metoprolol Succinate from Bulk Drugs. Asian J. Research Chem. 2009; 2(2): 119-122.
17. Venkatachalam T, et al. New Spectrophotometric Method Applied to the Simultaneous Determination of Metoprolol Succinate and Hydrochlorthiazide. Asian J. Research Chem. 2010; 3(2): 464-467.
18. Wankhede S, Dixit N, et al. Development and Validation of RP-HPLC Method for Quantitative Estimation of Atorvastatin Calcium and Metoprolol Succinate in Combined Dose Capsule Formulation. Asian J. Research Chem. 2010; 3(3): 663-665
19. Kanthale SB, Thonte SS and Mahapatra DK. Stability Indicating RP-HPLC Method for the simultaneous estimation of Ivabradine and Metoprolol in bulk and tablet formulation. J. of Applied Pharm. Sci. 2019; 9(4): 137-144.
20. Rahmani A, Selamat J and Soleimany F. Ochratoxin A and zearalenone using an experimental design, Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess. 2011; 28: 902-12.
21. Singh B, Raza K, Beg S. Developing “Optimized” Drug Products Employing “Designed” Experiments. Chem. Ind. Dig. 2013; 12, 1-7.
22. Monks KE, Rieger HJ and Molnar I. Expanding the term “Design Space” in high performance liquid chromatography (I). J. Pharm. Biomed. Anal. 2011; 56: 874-9.
23. Wu H and Khan MA. Quality‐by‐design (QbD): An integrated approach for evaluation of powder blending process kinetics and determination of powder blending end‐point. J. Pharm. Sci. 2009; 98: 2784-2798.
24. Schweitzer M, Pohl M, Hanna-Brown M. Implications and opportunities of applying QbD principles to analytical measurements. Pharmaceutical Technology. 2010; 34(2): 52–59.
25. Chavan S, Pimpodkar N, et al. Quality by Design. Asian J. Res. Pharm. Sci. 2016; 6(1): 45-50
26. Kadam V, Patil M, et al. A Review on: Quality by Design (QbD). Asian J. Res. Pharm. Sci. 2017; 7(4):197-204.
27. Kolekar Y. Understanding of DoE and its advantages in Pharmaceutical development as per QbD Approach. Asian J. Pharm. Tech. 2019; 9 (4):271-275