Author(s):
Patil Bhagyashri Sunil, Javesh. K. Patil, Chaudhari Hemangi Somnath, Patil Bhagyashri Sandip
Email(s):
bhagyashreep720@gmail.com , javesh4u@gmail.com
DOI:
10.52711/2231-5675.2025.00051
Address:
Patil Bhagyashri Sunil, Javesh. K. Patil, Chaudhari Hemangi Somnath, Patil Bhagyashri Sandip
P.S.G.V.P. Mandal’s College of Pharmacy, Shahada.
*Corresponding Author
Published In:
Volume - 15,
Issue - 4,
Year - 2025
ABSTRACT:
Benidipine Hydrochloride is a long-acting dihydropyridine calcium channel blocker (CCB) with a unique triple-blocking action on L-, T-, and N-type calcium channels. This distinct mechanism provides superior antihypertensive efficacy, cardiovascular protection, and renal benefits compared to conventional CCBs. Benidipine effectively lowers blood pressure by reducing peripheral vascular resistance while improving endothelial function and decreasing oxidative stress. Its ability to inhibit T-type calcium channels contributes to nephroprotection by lowering glomerular pressure and reducing proteinuria, making it particularly beneficial for patients with hypertension-related kidney disease. Additionally, N-type calcium channel blockade reduces sympathetic overactivity, leading to further stabilization of blood pressure and improved cardiac outcomes. Pharmacokinetically, Benidipine exhibits high lipophilicity, extensive plasma protein binding, and hepatic metabolism via CYP3A4, resulting in a prolonged half-life that supports once-daily dosing. Various analytical methods, including chromatographic techniques such as HPLC, UPLC, RP-HPLC, and LC-MS/MS, alongside spectroscopic techniques like UV-visible, FTIR, and NMR, are employed to assess its purity, stability, and pharmacokinetic properties. Advanced method development and validation strategies ensure regulatory compliance, drug safety, and therapeutic efficacy. This review explores Benidipine’s pharmacological profile, mechanism of action, and analytical methodologies, emphasizing its clinical significance in hypertension and cardiovascular disease management. Additionally, future trends in green chemistry and automation in pharmaceutical analysis are discussed, highlighting the evolving landscape of Benidipine research and its potential for improved therapeutic applications.
Cite this article:
Patil Bhagyashri Sunil, Javesh. K. Patil, Chaudhari Hemangi Somnath, Patil Bhagyashri Sandip; Benidipine Hydrochloride: A Triple-Action Calcium Channel Blocker for Superior Hypertension Management – Pharmacological Insights, Analytical Techniques, and Future Perspectives ; Asian Journal of Pharmaceutical Analysis. 2025; 15(4):328-3. doi: 10.52711/2231-5675.2025.00051
Cite(Electronic):
Patil Bhagyashri Sunil, Javesh. K. Patil, Chaudhari Hemangi Somnath, Patil Bhagyashri Sandip; Benidipine Hydrochloride: A Triple-Action Calcium Channel Blocker for Superior Hypertension Management – Pharmacological Insights, Analytical Techniques, and Future Perspectives ; Asian Journal of Pharmaceutical Analysis. 2025; 15(4):328-3. doi: 10.52711/2231-5675.2025.00051 Available on: https://ajpaonline.com/AbstractView.aspx?PID=2025-15-4-13
REFERENCES:
1. Yao K, Nagashima K, Miki H. Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker. J Pharmacol Sci. 2006 Apr; 100(4): 243–61.
2. Matsubara M, Yao K, Hasegawa K. Benidipine, a dihydropyridine-calcium channel blocker, inhibits lysophosphatidylcholine-induced endothelial injury via stimulation of nitric oxide release. Pharmacol Res. 2006 Jan; 53(1): 35–43.
3. Seino H, Miyaguchi S, Yamazaki T, Ota S, Yabe R, Suzuki S. Effect of benidipine hydrochloride, a long-acting T-type calcium channel blocker, on blood pressure and renal function in hypertensive patients with diabetes mellitus. Analysis after switching from cilnidipine to benidipine. Arzneimittelforschung. 2007; 57(8): 526–31.
4. Dohi Y, Kojima M, Sato K. Benidipine improves endothelial function in renal resistance arteries of hypertensive rats. Hypertens Dallas Tex 1979. 1996 Jul; 28(1): 58–63.
5. Yun HY, Yun MH, Kang W, Kwon KI. Pharmacokinetics and pharmacodynamics of benidipine using a slow receptor-binding model. J Clin Pharm Ther. 2005 Dec; 30(6): 541–7.
6. Abe M, Okada K, Maruyama N, Matsumoto S, Maruyama T, Fujita T, et al. Benidipine reduces albuminuria and plasma aldosterone in mild-to-moderate stage chronic kidney disease with albuminuria. Hypertens Res Off J Jpn Soc Hypertens. 2011 Feb; 34(2): 268–73.
7. Su JB. Vascular endothelial dysfunction and pharmacological treatment. World J Cardiol. 2015 Nov 26; 7(11): 719–41.
8. Mohini S, Rahul G. Sample Preparation for Pharmaceuticals using A Bioanalytical Method: A Review. Asian J Pharm Res. 2024 Sep 20; 14(3): 281–4.
9. Kako D, Ghareeb MM, Al-Lami MS. High-Performance Liquid Chromatography (HPLC) Method Validation for Identifying and Quantifying Rebamipide in Ethosomes. Cureus. 16(3): e56061.
10. Kako D, Ghareeb MM, Al-Lami MS. High-Performance Liquid Chromatography (HPLC) Method Validation for Identifying and Quantifying Rebamipide in Ethosomes. Cureus. 16(3): e56061.
11. Development and Validation of Analytical RP HPLC Method for Benidipine Hydrochloride. ResearchGate [Internet]. 2024 Oct 22 [cited 2025 Mar 6]; Available from: https://www.researchgate.net/publication/361350561_Development_and_Validation_of_Analytical_RP_HPLC_Method_for_Benidipine_Hydrochloride
12. Ultra Performance Liquid Chromatography - an overview | ScienceDirect Topics [Internet]. [cited 2025 Mar 6]. Available from: https://www.sciencedirect.com/topics/chemistry/ultra-performance-liquid-chromatography
13. ResearchGate [Internet]. 2024 [cited 2025 Mar 6]. (PDF) Review On: RP-HPLC. Available from: https://www.researchgate.net/publication/386262569_Review_On_RP-HPLC
14. Attimarad M, Ahmed KKM, Aldhubaib BE, Harsha S. High-performance thin layer chromatography: A powerful analytical technique in pharmaceutical drug discovery. Pharm Methods. 2011; 2(2): 71–5.
15. (PDF) Overview of High-Performance Thin Layer Chromatography and its Applications in Pesticide Analysis. ResearchGate [Internet]. 2024 Dec 9 [cited 2025 Mar 6]; Available from: https://www.researchgate.net/publication/366615191_Overview_of_High-Performance_Thin_Layer_Chromatography_and_its_Applications_in_Pesticide_Analysis
16. Kang W, Yun HY, Liu KH, Kwon KI, Shin JG. Determination of benidipine in human plasma using liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jun 15;805(2):311–4.
17. (Pdf) Development of UV Spectrophotometric Method for The Determination of Benidipine Hydrochloride by Using Quality by Design (Qbd) Approach. ResearchGate [Internet]. 2024 Oct 22 [cited 2025 Mar 6]; Available from: https://www.researchgate.net/publication/326350611_Development_Of_Uv_Spectrophotometric_Method_For_The_Determination_Of_Benidipine_Hydrochloride_By_Using_Quality_By_Design_Qbd_Approach
18. Chew YL, Khor MA, Lim YY. Choices of chromatographic methods as stability indicating assays for pharmaceutical products: A review. Heliyon. 2021 Mar 27; 7(3): e06553.
19. Fourier Transform Infrared Spectroscopy (FTIR) Analysis [Internet]. [cited 2025 Mar 6]. Available from: https://www.intertek.com/analytical-laboratories/ftir/
20. Bellur Atici E, Karlığa B. Identification, synthesis and characterization of process related impurities of benidipine hydrochloride, stress-testing/stability studies and HPLC/UPLC method validations. J Pharm Anal. 2015 Aug; 5(4): 256–68.
21. Pandya A, Howard MJ, Zloh M, Dalby PA. An Evaluation of the Potential of NMR Spectroscopy and Computational Modelling Methods to Inform Biopharmaceutical Formulations. Pharmaceutics. 2018 Sep 21; 10(4):165.
22. (PDF) Environmental benign RP-HPLC method for the simultaneous estimation of anti-hypertensive drugs using analytical quality by design. ResearchGate [Internet]. 2024 Oct 22 [cited 2025 Mar 6]; Available from: https://www.researchgate.net/publication/370984777_Environmental_benign_RP-HPLC_method_for_the_simultaneous_estimation_of_anti-hypertensive_drugs_using_analytical_quality_by_design
23. Abraham J. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. In: Tietje C, Brouder A, editors. Handbook of Transnational Economic Governance Regimes [Internet]. Brill | Nijhoff; 2010 [cited 2025 Mar 6]. p. 1041–53. Available from: https://brill.com/view/book/edcoll/9789004181564/Bej.9789004163300.i-1081_085.xml
24. (PDF) Application of a system suitability test for quality assurance and performance optimisation of a gas chromatographic system for pesticide residue analysis. ResearchGate [Internet]. 2024 Dec 4 [cited 2025 Mar 6]; Available from: https://www.researchgate.net/publication/8689795_Application_of_a_system_suitability_test_for_quality_assurance_and_performance_optimisation_of_a_gas_chromatographic_system_for_pesticide_residue_analysis
25. Shaikhmulani HI, Tamboli AM, Tamboli NA, Kshirsagar RT, Khandare O. RP-HPLC Method Development and Validation for Simultaneous Estimation of Benidipine Hydrochloride and Chlorthalidone in Pharmaceutical Dosage Form.
26. Naim M, Ahmed A, Gj K. Stability Indicating Reverse-Phase High- Performance Liquid Chromatography Method Development and Validation for Simultaneous Estimation of Telmisartan and Benidipine Hydrochloride in Pharmaceutical Dosage Form. Asian J Pharm Clin Res. 2018 May 1; 11(5): 342.
27. Mujawar T, Ahmad S, Gadilohar H, Deshmukh N, Gaikwad A, Sable V, et al. Analytical method development and validation for the simultaneous estimation of Metoprolol and Benidipine by RP-HPLC in bulk and tablet dosage forms. Int J Health Sci. 2022 Aug 30; 8188–202.
28. Kadam MM, Pakhare RD, Ambhore b. Development and validation of rp- hplc method for estimation of benidipine in bulk and tablet dosage form. 2023; 11(6).
29. Jain PG, Chaudhary AB, Bhadani sm. Development and validation of RP-HPLC method for simultaneous estimation of benidipine hydrochloride and telmisartan in tablet.
30. Dharuman N, Lakshmi KS, Krishnan M. Environmental benign RP-HPLC method for the simultaneous estimation of anti-hypertensive drugs using analytical quality by design. Green Chem Lett Rev. 2023 Jan 2; 16(1): 2214176.
31. Patel DM, Patel D, Patel A, Sheth A, Shah UJ. Method Development and Validation for Simultaneous Estimation of Benidipine Hydrochloride and Metoprolol Succinate in Tablet. J Drug Deliv Ther. 2019 Dec 15; 9(6-s): 28–33.
32. Jagadeesh K, Annapurna N. Stability Indicating Method to Analyze Benidipine and Chlorthalidone Using HPLC Technique: Establishment, Validation and Application to Tablets. Pharm Sci. 2020 Mar 10; 26(1): 75–81.
33. Patel B, Chaudhary A, Gami S. RP-HPLC Method Development and Validation for Simultaneous Estimation of Benidipine Hydrochloride, Telmisartan and Chlorthalidone in Tablet [Internet]. Rochester, NY: Social Science Research Network; 2019 [cited 2025 Mar 6]. Available from: https://papers.ssrn.com/abstract=3553661