Physical and Chemical Properties and Methods of Control of Pantoprazol Sodium Sesquihydrate (Review)

Introduction. Pantoprazole sodium sesquihydrate is a proton pump inhibitor. This substance is used in the treatment of peptic ulcer of the duodenum or stomach in the acute phase, including those associated with the use of non-steroidal anti-inflammatory drugs.

Text. Pantoprazole is sodium 5-(difluoromethoxy)-2-[(RS)-[(3,4-dimethoxypyridin-2-yl)methyl]sulfinyl]benzimidazol-1-ide sesquihydrate in its structure. The substance is readily soluble in water and ethyl alcohol. The identification of pantoprazole is confirmed by infrared absorption spectrophotometry, as well as by a positive reaction to sodium ion. For the assay of this substance chemical and physico-chemical methods are used. The first group of methods includes titration in a non-aqueous medium with perchloric acid and permanganatometry. Physico-chemical methods used for pantoprazole assay are spectrophotometry and HPLC. The most commonly used method is direct spectrophotometry associated with the measurement of optical density at a wavelength of the maximum absorption of pantoprazole in various solvents. In addition, spectrophotometric methods of assay are known, based on the study of the absorption of colored pantoprazode reaction products. The derivative spectrophotometry is used for the analysis of its preparations. The control of the content of impurities and pantoprazole in the substance and its dosage forms is carried out, as a rule, using HPLC.

Conclusion. An analysis of the literature has shown that this substance is unstable. Therefore, this feature of pantoprazole must be considered when choosing excipients when developing a dosage form. The preferred method for analyzing pantoprazole preparations is HPLC, since it is possible to determine the substance in the presence of other compounds, which will allow one to control the quantitative content and stability of pantoprazole in the preparation.

1. Пантопразол. Available at: https://www.rlsnet.ru/mnn_index_id_2670.htm (дата обращения 03.12.2019).

2. Priya D. S., Prashanthi K., Parijatha B., Mohan C. K. Validation of stability indicating LC-MS assay method for determination of pantoprazole sodium sesquihydrate. World journal of pharmacy and pharmaceutical sciences. 2017; 6(1): 1413–1426.

3. Издание Европейской Фармакопеи на русском языке. VII изд. В 2 т. М.: ООО «Ремедиум». 2011: 4504.

4. Badwan A. A., Nabulsi L. N., Omari M. M. A. et al. Pantoprazole Sodium. Analytical Profiles of Drug Substances and Excipients. 2002; 29: 213–259. DOI: 10.1016/s1075-6280(02)29008-4.

5. Kumar R., Singh H., Singh P. Development of UV Spectrophotometric method for estimation of Pantoprazole in pharmaceutical dosage forms. J. Chem. Pharm. Res. 2011; 3(2): 113–117.

6. Shinde V., Sarode V., Kshirsagar S., Jadhav A. Development and validation of UV Spectrophotometric method for estimation of pantoprazole sodium in bulk and tablet dosage form. CIBTech Journal of Pharmaceutical Sciences. 2016; 5(4): 22–26.

7. Süslü İ., Altinöz S., Yildiz E. Determination of Pantoprazole in Tablet Dosage Forms by Two Different Spectrophotometric Methods. FABAD J. Pharm. Sci. 2003; 28: 85–92.

8. Patil S. S., Dhabale P. N., Kuchekar B. S. Spectrophotometric estimation of pantoprazole in tablet dosage form. Int. J. Chem. Sci. 2008; 6(4): 1984–1990.

9. Rahman N., Kashif M. Initial-rate method for the determination of pantoprazole in pharmaceutical formulations using 1-fluoro 2,4-dinitrobenzene. Pharmazie. 2005; 60(3): 197–200.

10. Devi O. Z., Basavaiah K., Vinay K. B. Sensitive and selective spectrophotometric determination of pantoprazole sodium in pharmaceuticals using permanganate. Chemical Industry and Chemical Engineering Quarterly. 2010; 16(1): 97–102. DOI: 10.2298/ciceq091006015d.

11. Basavaiah K., Rajendraprasad N., Tharpa K. et al. Titrimetric and Spectrophotometric Assay of Pantoprazole in Pharmaceuticals Using Permanganate. J. Mex. Chem. Soc. 2009; 53(1): 34–40. DOI: 10.29356/jmcs.v53i1.1015.

12. Rangachar U., Kumar A., Basavaiah K. Sensitive and validated spectrophotometric methods for the determination of pantoprazole sodium in pharmaceuticals using n-bromosuccinimide based on redox and complexation reactions. Bull. Chem. Soc. Ethiop. 2008; 22(1): 135–141. DOI: 10.4314/bcse.v22i1.61350.

13. Devi O. Z., Basavaiah K. Validated spectrophotometric determination of pantoprazole sodium in pharmaceuticals using ferric chloride and two chelating agents. International Journal of ChemTech Research. 2010; 2(1): 624–632.

14. Rahman N., Bano Z., Azmi S. N. H. Kinetic Spectrophotometric Analysis of Pantoprazole in Commercial Dosage Forms. Analytical sciences. 2006; 22: 983–988. DOI: 10.2116/analsci.22.983.

15. Gupta K. R., Chawla R. B., Wadodkar S. G. Stability indicating RP-HPLC method for simultaneous determination of pantoprazole sodium and itopride hydrochloride in bulk and capsule. Orbital Elec. J. Chem. 2010; 2(3): 209–224.

16. Johnson C. E. Stability of Pantoprazole in 0.9 % Sodium Chloride Injection in Polypropylene Syringes. Am J Health Syst Pharm. 2005; 62(22): 2410–2412. DOI: 10.2146/ajhp050132.

17. Donnelly R. F. Stability of Pantoprazole Sodium in Glass Vials, Polyvinyl Chloride Minibags, and Polypropylene Syringes. CJHP. 2011; 64(3): 192–198. DOI: 10.4212/cjhp.v64i3.1022.

18. Kothapalli L. P., Inamdar A. A., Nanda R. K., Thomas A. B. Development and validation of a stability indicating RP-HPLC method for simultaneous estimation of Pantoprazole sodium sesquihydrate and Levosulpiride in a combined dosage form. Int J Res Pharm Sci. 2014; 4(4): 32–38.

19. Souri E., Ravari N. S., Alvandifar F. et al. Validated Stability-Indicating HPLC Method for the Determination of Pantoprazole in the Presence of Its Degradation Products. Asian Journal of Research in Chemistry. 2010; 3(4): 879–884.

20. Mishra P. K., Upadhyay S., Tripathi A. C., Saraf S. K. Stability Indicating HPLC-UV Method for Simultaneous Estimation of Pantoprazole, Domperidone and Drotaverine. Int. J. PharmTech Res. 2015; 8(5): 912–923.

21. Pandey S., Pandey P., Mishra D., Singh U. K. A validated stability indicating HPLC method for the determination of process-related impurities in pantoprazole bulk drug and formulations. Brazilian Journal of Pharmaceutical Sciences. 2013; 49(1): 175–184. DOI: 10.1590/s1984-82502013000100019.

22. Sree J. V., Rajappan M., Kannappan V. Stability-indicating HPLC method for the simultaneous determination of pantoprazole, rabeprazole, lansoprazole and domperidone from their combination dosage forms. International Journal of Drug Development & Research. 2011; 3(4): 323–335.