A Novel and Sensitive Spectrophotometric Approach for Quantifying Vardenafil Hydrochloride Trihydrate in Tablets: Application to Dissolution Testing
Abstract
Aims: To develop and validate a novel Zero-order Absorbance UV-Spectrophotometric method for the quantification of Vardenafil Hydrochloride Trihydrate in commercial tablets and its application for dissolution testing.
Background: Erectile Dysfunction (ED) is a significant disorder affecting men's sexual health, with Vardenafil being a potent and selective inhibitor of phosphodiesterase type 5 (PDE5). Vardenafil is commonly used as an oral therapy for treating ED. Accurate and reliable methods for its quantification in pharmaceutical formulations and during dissolution tests are essential for quality control.
Objective: To establish and validate a simple, accurate, precise, economical, and sensitive method for determining the concentration of Vardenafil hydrochloride trihydrate in commercial tablets and during dissolution tests using UV-Spectrophotometry.
Method: A Zero-order Absorbance UV-Spectrophotometric approach was employed, utilizing 0.1N HCl as the solvent. The method was optimized to determine Vardenafil hydrochloride trihydrate within a linear range of 2-12 µg/mL, with a coefficient of correlation value greater than 0.99. The method was validated for accuracy, precision, sensitivity, and ruggedness according to ICH guidelines. Additionally, the method was applied for the quantification of Vardenafil hydrochloride trihydrate in dissolution tests.
Result: The method successfully determined Vardenafil hydrochloride trihydrate concentration in commercial tablets, showing a % recovery between 99.85% and 100.07%. The % amount of drug estimated was in good agreement with the label claims. The method also allowed direct measurement of samples from the dissolution vessel without pH correction.
Conclusion: The developed UV-Spectrophotometric method is a reliable, accurate, and cost-effective approach for quantifying Vardenafil hydrochloride trihydrate in commercial tablets and during dissolution tests. The method's validation as per ICH guidelines ensures its suitability for routine quality control.
Other: This analytical approach provides the simple and economical technique for the analysis of Vardenafil hydrochloride in pharmaceutical formulation.
References
2. Althof, S.E., 2002. Quality of life and erectile dysfunction. Urology, 59(6), pp.803-810.
3. Rosen, R.C. and Kostis, J.B., 2003. Overview of phosphodiesterase 5 inhibition in erectile dysfunction. The American journal of cardiology, 92(9), pp.9-18.
4. Rosen, R.C. and McKenna, K.E., 2002. PDE-5 inhibition and sexual response: pharmacological mechanisms and clinical outcomes. Annual review of sex research, 13(1), pp.36-88.
5. Saikia, Q., Hazarika, A. and Mishra, R., 2022. A review on the pharmacological importance of PDE5 and its inhibition to manage biomedical conditions. Journal of Pharmacology and Pharmacotherapeutics, 13(3), pp.246-257.
6. Burnett, A.L. and Musicki, B., 2005. The nitric oxide signaling pathway in the penis. Current pharmaceutical design, 11(31), pp.3987-3994.
7. Huang, S.A. and Lie, J.D., 2013. Phosphodiesterase-5 (PDE5) inhibitors in the management of erectile dysfunction. Pharmacy and therapeutics, 38(7), p.407.
8. Gur, S., J Kadowitz, P., Gokce, A., C Sikka, S., Lokman, U. and JG Hellstrom, W., 2013. Update on drug interactions with phosphodiesterase-5 inhibitors prescribed as first-line therapy for patients with erectile dysfunction or pulmonary hypertension. Current drug metabolism, 14(2), pp.265-269.
9. Sweetman, S.C. 2011. Martindale. The complete drug reference, 38th ed. London: Pharmaceutical Press, pp. 2372.
10. Cheng, C.L., Kang, G.J. and Chou, C.H., 2007. Development and validation of a high-performance liquid chromatographic method using fluorescence detection for the determination of vardenafil in small volumes of rat plasma and bile. Journal of Chromatography A, 1154(1-2), pp.222-229.
11. Aboul‐Enein, H.Y., Ghanem, A. and Hoenen, H., 2005. Determination of vardenafil in pharmaceutical formulation by HPLC using conventional C18 and monolithic silica columns. Journal of liquid chromatography & related technologies, 28(4), pp.593-604.
12. Carlucci, G., Palumbo, P., Iuliani, P. and Palumbo, G., 2009. Development of a method for the determination of vardenafil in human plasma by high performance liquid chromatography with UV detection. Biomedical Chromatography, 23(7), pp.759-763.
13. Ding, M., Wu, X., Yuan, L., Wang, S., Li, Y., Wang, R., Wen, T., Du, S. and Zhou, X., 2011. Synthesis of core–shell magnetic molecularly imprinted polymers and detection of sildenafil and vardenafil in herbal dietary supplements. Journal of hazardous materials, 191(1-3), pp.177-183.
14. Fejős, I., Neumajer, G., Béni, S. and Jankovics, P., 2014. Qualitative and quantitative analysis of PDE-5 inhibitors in counterfeit medicines and dietary supplements by HPLC–UV using sildenafil as a sole reference. Journal of Pharmaceutical and Biomedical Analysis, 98, pp.327-333.
15. Nickum, E.A. and Flurer, C.L., 2015. Determination of phosphodiesterase-5 inhibitors and analogs using high-performance liquid chromatography with ultraviolet detection. Journal of chromatographic science, 53(1), pp.38-46.
16. Mohamad, S.A., Mustafa, W.W., Salem, H., Elrehany, M., Rofaeil, R.R. and Abdelkader, H., 2022. Physicochemical characteristics and ex vivo skin permeability for three phosphodiesterase 5 inhibitors (sildenafil, tadalafil and vardenafil): A proof-of-concept study for topical penile therapy. Journal of Drug Delivery Science and Technology, 70, p.103166.
17. Sacré, P.Y., Deconinck, E., Chiap, P., Crommen, J., Mansion, F., Rozet, E., Courselle, P. and De Beer, J.O., 2011. Development and validation of a ultra-high-performance liquid chromatography-UV method for the detection and quantification of erectile dysfunction drugs and some of their analogues found in counterfeit medicines. Journal of chromatography A, 1218(37), pp.6439-6447.
18. Satheesh, B., Sree Ganesh, K.K. and Saravanan, D., 2013. Simultaneous determination of tadalafil and its related compounds in pharmaceutical dosage forms by UPLC. Journal of Liquid Chromatography & Related Technologies, 36(10), pp.1451-1465.
19. De Orsi, D., Pellegrini, M., Marchei, E., Nebuloni, P., Gallinella, B., Scaravelli, G., Martufi, A., Gagliardi, L. and Pichini, S., 2009. High performance liquid chromatography-diode array and electrospray-mass spectrometry analysis of vardenafil, sildenafil, tadalafil, testosterone and local anesthetics in cosmetic creams sold on the Internet web sites. Journal of pharmaceutical and biomedical analysis, 50(3), pp.362-369.
20. Osypchuk, L., Halkevych, I., Davydovych, S. and Bidnychenko, Y., 2019. Validation of an HPLC-MS method for the determinatin of vardenafil in rat urine. J Appl Pharm Sci, 9(08), pp.079-085.
21. Rust, K.Y., Wilkens, H., Kaiser, R., Bregel, D., Wilske, J. and Kraemer, T., 2012. Detection and Validated Quantification of the Phosphodiesterase Type 5 Inhibitors Sildenafil, Vardenafil, Tadalafil, and 2 of Their Metabolites in Human Blood Plasma by LC-MS/MS─ Application to Forensic and Therapeutic Drug Monitoring Cases. Therapeutic drug monitoring, 34(6), pp.729-735.
22. Savaliya, A.A., Shah, R.P., Prasad, B. and Singh, S., 2010. Screening of Indian aphrodisiac ayurvedic/herbal healthcare products for adulteration with sildenafil, tadalafil and/or vardenafil using LC/PDA and extracted ion LC–MS/TOF. Journal of pharmaceutical and biomedical analysis, 52(3), pp.406-409.
23. Gratz, S.R., Flurer, C.L. and Wolnik, K.A., 2004. Analysis of undeclared synthetic phosphodiesterase-5 inhibitors in dietary supplements and herbal matrices by LC–ESI–MS and LC–UV. Journal of Pharmaceutical and Biomedical Analysis, 36(3), pp.525-533.
24. De Orsi, D., Pellegrini, M., Marchei, E., Nebuloni, P., Gallinella, B., Scaravelli, G., Martufi, A., Gagliardi, L. and Pichini, S., 2009. High performance liquid chromatography-diode array and electrospray-mass spectrometry analysis of vardenafil, sildenafil, tadalafil, testosterone and local anesthetics in cosmetic creams sold on the Internet web sites. Journal of pharmaceutical and biomedical analysis, 50(3), pp.362-369.
25. Zou, P., Oh, S.S.Y., Hou, P., Low, M.Y. and Koh, H.L., 2006. Simultaneous determination of synthetic phosphodiesterase-5 inhibitors found in a dietary supplement and pre-mixed bulk powders for dietary supplements using high-performance liquid chromatography with diode array detection and liquid chromatography–electrospray ionization tandem mass spectrometry. Journal of Chromatography A, 1104(1-2), pp.113-122
26. Unceta, N., Echeazarra, L., Montaña, M., Sallés, J., Gómez-Caballero, A., Goicolea, M.A. and Barrio, R.J., 2012. Validation of an LC–ESI-MS/MS method for the quantitation of phosphodiesterase-5 inhibitors and their main metabolites in rat serum and brain tissue samples. Journal of pharmaceutical and biomedical analysis, 70, pp.529-533.
27. Lee, E.S., Lee, J.H., Han, K.M., Kim, J.W., Hwang, I.S., Cho, S., Han, S.Y. and Kim, J., 2013. Simultaneous determination of 38 phosphodiestrase-5 inhibitors in illicit erectile dysfunction products by liquid chromatography–electrospray ionization-tandem mass spectrometry. Journal of pharmaceutical and biomedical analysis, 83, pp.171-178.
28. Zhu, X., Xiao, S., Chen, B., Zhang, F., Yao, S., Wan, Z., Yang, D. and Han, H., 2005. Simultaneous determination of sildenafil, vardenafil and tadalafil as forbidden components in natural dietary supplements for male sexual potency by high-performance liquid chromatography–electrospray ionization mass spectrometry. Journal of Chromatography A, 1066(1-2), pp.89-95.
29. Guo, J.B., Xu, Y., Huang, Z.B., He, Q.H. and Liu, S.W., 2010. Development of an immunoassay for rapid screening of vardenafil and its potential analogues in herbal products based on a group specific monoclonal antibody. Analytica chimica acta, 658(2), pp.197-203.
30. Abdelshakour, M.A., Salam, R.A.A., Hadad, G.M., Abo-ElMatty, D.M. and Hameed, E.A.A., 2021. HPLC-UV and UPLC-MS/MS methods for the simultaneous analysis of sildenafil, vardenafil, and tadalafil and their counterfeits dapoxetine, paroxetine, citalopram, tramadol, and yohimbine in aphrodisiac products. RSC Advances, 11(14), pp.8055-8064.
31. Chapla, B., Amin, G., Pandya, A., Kakadiya, J. and Shah, N., 2012. Simultaneous estimation and validation of vardenafil and dapoxetine hydrochloride in pharmaceutical formulation by thin layer chromatographic densitometric method. Int Res J Pharm, 3(5), pp.480-483.
32. Septiani, R. and Damayanti, S., 2015. Simultaneous identification of caffeine acetaminophen, sildenafilcitrate, tadalafil and vardenafil HCl in aphrodisiac traditional herbal medicines by Thin Layer Chromatography-Densitometry. Der. Pharma. Chemica, 7(5), pp.335-341.
33. Do, T.T., Theocharis, G. and Reich, E., 2015. Simultaneous detection of three phosphodiesterase type 5 inhibitors and eight of their analogs in lifestyle products and screening for adulterants by high-performance thin-layer chromatography. Journal of AOAC International, 98(5), pp.1226-1233.
34. El Shiekh, R., Amin, A.S., Hafez, E.M. and Gouda, A.A., 2016. Spectrophotometric estimation of vardenafil HCl and tadalafil in pure forms and tablets using cerium (IV) ammonium sulphate. Der Pharmacia Lettre, 8(15), pp.153-165.
35. Sakur, A.A. and Affas, S., 2017. Validated spectrophotometric method to determine vardenafil and sildenafil in pharmaceutical forms using potassium iodide and potassium iodate. Int J Pharm Pharm Sci, 9(11), pp.65-9.
36. Abdel-Gawad, Fatma & Abdelmoety, Mona & Mohamed, Ethar. (2017). Simultaneous Determination of Vardenafil and Dapoxetine Hydrochlorides in Combined Dosage Forms Using HPLC and UV- Spectrophotometric Methods.
37. Affas, S. and Sakur, A.A., 2019. Spectrophotometric Method for Simultaneous Estimation of Dapoxetine and some Phosphodiesterase-5 inhibitors in new combinations. Research Journal of Pharmacy and Technology, 12(11), pp.5193-5198.
38. Patel, B., Chaudhari, A. and Mashru, R., 2017. Development and validation of RP-HPLC and UV-spectroscopy for simultaneous estimation of vardenafil hydrochloride and sildenafil citrate. World J. Pharm. Pharm. Sci., 6(7), pp.1039-1049.
39. Ahmed, N.R., Ahmed, I.A. and Qasim, H.Y., 2020. Ultra-sensitive estimation of vardenafil. HCL in pharmaceutical preparations and environmental waste water samples. Eur. J. Biomed. Pharm. Sci, 7, pp.85-89.
40. Flores, J.R., Nevado, J.B., Penalvo, G.C. and Diez, N.M., 2004. Development of a micellar electrokinetic capillary chromatography method for the determination of three drugs employed in the erectile dysfunction therapy. Journal of Chromatography B, 811(2), pp.231-236.
41. Vidal, D.T.R., Augelli, M.A. and do Lago, C.L., 2013. Determination of sildenafil and vardenafil by capillary zone electrophoresis using capacitively coupled contactless conductivity detection. Analytical Methods, 5(8), pp.2041-2045.
42. Mokhtar, S.U., Chin, S.T., Kee, C.L., Low, M.Y., Drummer, O.H. and Marriott, P.J., 2016. Rapid determination of sildenafil and its analogues in dietary supplements using gas chromatography–triple quadrupole mass spectrometry. Journal of pharmaceutical and biomedical analysis, 121, pp.188-196.
43. Carlucci, G., Palumbo, P., Iuliani, P. and Palumbo, G., 2009. Development of a method for the determination of vardenafil in human plasma by high performance liquid chromatography with UV detection. Biomedical Chromatography, 23(7), pp.759-763.
44. Subba Rao, D.V., Surendranath, K.V., Radhakrishnanand, P., Suryanarayana, M.V. and Raghuram, P., 2008. A stability indicating LC method for vardenafil HCl. Chromatographia, 68(9), pp.829-835.
45. International Conference on Harmonization (ICH). Q2 (R1), Validation of Analytical Procedures: Text and Methodology; IFPMA: Geneva, 2005.