65.Issue 01 january 25 - INDO AMERICAN JOURNAL OF PHARMACEUTICAL SCIENCES

Volume : 12, Issue : 01, January – 2025

Title:

AN OVERVIEW ON NIRMATERELVIR DRUG FORMULATION BY RP-HPLC

Authors :

Gopal K. Malekar ,Vaibhav G. Akhand ,Vinayak A. Katekar, Swati P. Deshmukh

Abstract :

Nirmatrelvir is an antiviral drug primarily developed for the treatment of COVID-19, often co-administered with ritonavir to enhance its pharmacokinetic profile. This paper provides an overview of the formulation of Nirmatrelvir with a focus on its analytical characterization, particularly using Reverse Phase High-Performance Liquid Chromatography (RP-HPLC). RP-HPLC is a widely utilized technique for the quantification, purity assessment, and stability monitoring of pharmaceutical compounds due to its high sensitivity, specificity, and efficiency.
The formulation of Nirmatrelvir involves complex considerations to ensure bioavailability, stability, and efficacy. RP-HPLC serves as a crucial analytical tool in optimizing these formulations. In the context of Nirmatrelvir, RP-HPLC methods are employed to analyze the drug’s chemical stability, detect impurities, and monitor the concentration of active pharmaceutical ingredients (APIs). Key factors such as mobile phase composition, column selection, flow rate, and detection wavelength are optimized to achieve the best separation and accurate quantification of Nirmatrelvir.
Keywords: Nirmaterelvir(paxloid), Protease inhibitor, COVID-19 antiviral drug, SARS-Cov- inhibitor, Nirmaterelvir mechanism, Viral replication blocker, Nirmaterelvir pharmacology

Cite This Article:

Please cite this article in press Gopal K. Malekar et al., An Overview On Nirmaterelvir Drug Formulation By RP-HPLC., Indo Am. J. P. Sci, 2025; 12 (01).

Number of Downloads : 10

References:

1. Aboras, S. I., and M. M. Hadir. “Green Adherent Degradation Kinetics Study of Nirmatrelvir, an Oral Anti-COVID-19: Characterization of Degradation Products Using LC-MS with In Silico Toxicity Profile.” BMC Chemistry, vol. 17, no. 1, 2023, p. 23.
2. Babu, V. S., and H. K. Sharma. “Method Development and Validation of Ritonavir and Nirmatrelvir in Tablet Dosage Form by Using RP-High Performance Liquid Chromatography.” European Chemical Bulletin, vol. 12, special issue 5, 2023, pp. 815-25.
3. Carlin, A. F., A. E. Clark, A. Chaillon, et al. “Virologic and Immunologic Characterization of Coronavirus Disease 2019.”
4. Chatterjee, S., et al. “Resistance to Nirmatrelvir Due to Mutations in the Mpro in the Subvariants of SARS-CoV-2 Omicron: Another Concern?” Molecular Therapy – Nucleic Acids, 2023.
5. Chenxi, L., M. Q. Z., et al. “Simultaneous Determination of Nirmatrelvir and Ritonavir in Human Plasma Using LC-MS/MS and Its Pharmacokinetic Application in Healthy Chinese Volunteers.” Biomedical Chromatography, vol. 36, no. 11, 2022.
6. Chiranjeevi, K., and K. P. Channabasavaraj. “Development and Validation of RP-HPLC Method for Quantitative Estimation of Ritonavir in Bulk and Pharmaceutical Dosage Forms.” International Journal of Pharmaceutical Sciences Review and Research, vol. 2, no. 3, 2011.
7. Choudhary, M. I., M. Shaikh, A. T. Wahab, and D. Salahub. “In Silico Identification of Potential Inhibitors of Key SARS-CoV-2 3CL Hydrolase (Mpro) via Molecular Docking, MMGBSA Predictive Binding Energy Calculations, and Molecular Dynamic Simulation.” PLOS ONE, July 2020.
8. Hammond, J., et al. “Oral Nirmatrelvir for High-Risk Nonhospitalized Adults with COVID-19.” New England Journal of Medicine, 2022.
9. Hashemian, S. M. R., A. Sheida, M. Taghizadieh, et al. “Paxlovid (Nirmatrelvir/Ritonavir): A New Approach to COVID-19.”
10. “ICH Q2A Text on Analytical Method Validation.” International Conference on Harmonization, Geneva, 1991, pp. 1-5.
11. “ICH Q2B Validation of Analytical Procedure.” International Conference on Harmonization, Geneva, 1996, pp. 1-8.
12. Ilayaraja, P., M. Manivannan, and P. Parthiban. “Novel Stability Indicating HPLC Method for the Quantification of Nirmatrelvir in Bulk Drugs.” Microchemical Journal, vol. 196, 2024, p. 109707.
13. Kumar, G. S., and M. B. Kumar. “Development and Validation of RP-HPLC Method for the Simultaneous Determination of Nirmatrelvir and Ritonavir in Bulk and Pharmaceutical Formulation.” Research Journal of Chemistry and Environment, vol. 27, no. 4, 2023, pp. 120-27.
14. Martens-Lobenhoffer, J., C. R. Boger, et al. “Simultaneous Quantification of Nirmatrelvir and Ritonavir by LC-MS/MS in Patients Treated for COVID-19.” Journal of Chromatography B, vol. 1212, 2022, p. 123510.
15. Mohamed, S. I., S. B. Afnan, et al. “Adjusted Green HPLC Determination of Nirmatrelvir and Ritonavir in the New FDA Approved Co-Packaged Pharmaceutical Dosage Using Supported Computational Calculations.” Scientific Reports, vol. 13, no. 1, 2023, p. 137.
16. Nassar, A., I. M. Ibrahim, F. G. Amin, M. Magdy, A. M. Elgharib, E. B. Azzam, F. Nasser, K. Yousry, I. M. Shamkh, S. M. Mahdy, A. A. Elfiky. “A Review of Human Coronaviruses’ Receptors: The Host-Cell Targets for the Crown Bearing Viruses.” Molecules, vol. 26, no. 21, 2021, p. 6455.
17. Pallavi, S., and G. Sowjanya. “Development and Validation of a New RP-UPLC Method for the Simultaneous Estimation of Nirmatrelvir and Ritonavir in Bulk and Co-Packaged Tablet Dosage Forms.” Research Journal of Pharmaceutical Technology, vol. 16, no. 9, 2023, pp. 4370-76.
18. Rani, D. J. B., and C. A. Deepti. “Development of a Simple Accurate Method, Validation and Its Degradation Studies of Nirmatrelvir, Ritonavir in Bulk and Marketed Formulation by RP-HPLC.” International Journal of Pharmaceutical Quality Assurance, vol. 14, no. 3, September 2023.
19. Saramago, L. C., et al. “AI-Driven Discovery of SARS-CoV-2 Main Protease Fragment-Like Inhibitors with Antiviral Activity in Vitro.” Journal of Chemical Information and Modeling, 2023.
20. Singh, R. S. P., et al. “Innovative Randomized Phase I Study and Dosing Regimen Selection to Accelerate and Inform Pivotal COVID-19 Trial of Nirmatrelvir.” Clinical Pharmacology and Therapeutics, 2022.
21. Weil, T., et al. “Immunodetection Assays for the Quantification of Seasonal Common Cold Coronaviruses OC43, NL63, or 229E Infection Confirm Nirmatrelvir as Broad Coronavirus Inhibitor.” Antiviral Research, 2022.
22. Zhang, L., D. Lin, X. Sun, U. Curth, C. Drosten, L. Sauerhering, and R. Hilgenfeld. “Crystal Structure of SARS-CoV-2 Main Protease Provides a Basis for Design of Improved α-Ketoamide Inhibitors.” Science, 2020.
23. Yang, H., W. Xie, X. Xue, K. Yang, J. Ma, W. Liang, Q. Zhao, Z. Zhou, D. Pei, J. Ziebuhr, et al. “Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases.” PLOS Biology, vol. 3, e324, 2005.
24. Owen, D. R., C. M. N. Allerton, A. S. Anderson, L. Aschenbrenner, M. Avery, S. Berritt, B. Boras, R. D. Cardin, A. Carlo, K. J. Coffman, et al. “An Oral SARS-CoV-2 M(pro) Inhibitor Clinical Candidate for the Treatment of COVID-19.” Science, vol. 374, 2021, pp. 1586-93.
25. Razali, R., H. Asis, and C. Budiman. “Structure-Function Characteristics of SARS-CoV-2 Proteases and Their Potential Inhibitors from Microbial Sources.” Microorganisms, vol. 9, no. 2481, 2021.
26. Yang, K. S., S. Z. Leeuwon, S. Xu, and W. R. Liu. “Evolutionary and Structural Insights about Potential SARS-CoV-2 Evasion of Nirmatrelvir.” Journal of Medicinal Chemistry, vol. 65, 2022, pp. 8686-98.