INTRODUCTION:

Lacidipine is a 1, 4 dihydropyridine class of a drug and is widely used as a calcium channel blocker andused as anti- anginal drug and antihypertensive drug. It shows anti-atherosclerotic and antioxidant effects. Lacidipine is available in tablet form and is marketed under various brand names such as Caldine, Lacimen, Lacipil, Midotens, and Motens. It has long duration of action because of its high degree of lipophilicity.¹ Lacidipine has a molecular formula of C₂₆H₃₃NO₆ and a molecular weight of 455.54g/mol². It shows some physicochemical properties. Like Solubility, i.e. Lacidipine is slightly soluble in water and it is more soluble in solvents such as ethanol, methanol, acetone, Dimethyl Sulphoxide (DMSO). Lacidipine absorbs light in the wavelength at 240nm. It is highly sensitive to the action of temperature and light.³ It attempt has to develop new UV method for its estimation in bulk and pharmaceutical formulations withtheir good accuracy, simplicity, precision and economy.

Trans form is used in therapy.⁴ Lacidipine or its metabolite inhibits the angiotensin converting enzyme (ACE) and other hormone receptors or ion channels.⁵ Various methods have been reported for the quantitative and qualitative determination of Lacivas 2mg tablets including spectrophotometry. Whereas RP-LC was used for the stability study of Lacidipine towards light, temperature and humidity.⁶ It undergoes extensive first-pass hepatic metabolism having shown result to a low oral bioavailability was found about 10%. It has high degree of lipophilicity because of its long duration of action. Lacidipine estimatedby various analytical methods. LC-DAD, UPLC-TMS, HPTLC, HPLC, LC-MS, UV and Electrochemical methods to develop a new Ultra violet spectrophotometric method used for identification of Lacidipine in pharmaceutical dosage form.

Structure of Lacidipine

Brand Names of Lacidipine:

1. LACIVAS tab manufactured by Sun Pharma.

2. SINOPIL tab manufactured by Glaxo Smith Kline.

Molecular Weight - 455.55 g/mol.

Molecular Formula - C₂₆H₃₃NO₆

Analytical Methods Reported For The Estimation of Lacidipine:

1. Arivozhi Mohan et al in the year 2011 had been reported to develop RP-UPLC method for the chromatographic separation was achieved by using BEH C18 column with their PH 4.5 and also validated for the determination of lacidipine by using a simple isocratic, solution. Using the Mobile phase like ammonium acetate–acetic acid buffer– methanol (70 + 30, v/v). There are three process of impurities and three degradation products. It formed during synthesis of drug substance having wavelength used at 240nm. And the flow rate 0.25mL/min. The method was validated i.e. Parameters like specificity, precision, linearity, accuracy, LOD, LOQ, and robustness, according to ICH guidelines. Forced degradation studies using such as acid, alkali, peroxide, water, heat, and light were used, and impurities are carried out.⁷

2. K.P. Channabasavaraj Nagaraju et al in the year 2010 to develop the number of analytical methods used for estimation of lacidipine by using LC-DAD, HPTLC, LC-MS, and UV method. Only one HPLC method was developed and determined by the biological fluids in lacidipine drug. It was to develop a RP-HPLC method for analysis of the drug in pharmaceutical dosage forms. It include the simple composition of mobile phase.⁸

3. Rajavel A, Sanmuga priya et al in the year 2011 had been to developed and reported for the spectrophotometry of lacidipine drug by using the quantitative analysis. Include that stability studies for RP-LC method and used for lacidipine drug towards the moisture content, temperature and light.it has been develop a method using the RP-HPLC. Used to determine the trace level of lacidipine it caused by temperature, base, peroxide, light and acid etc. for the frequent impurities.⁹

4. Nagaraju P.T. et al in the year 2011 had been reported number of analytical methods used for estimation of lacidipine by using like LC-DAD, HPLC, UV, LC-MS, HPTLC method. Also apart from the above methods no other spectroscopic methods i.e. RP-HPLC, UV visible, and different spectrophotometric method by using the internal standards etc. It estimates different validated parameters used to develop the UV spectrophotometric method by using the bulk drug and its pharmaceutical formulation.etc. Having with good accuracy, simplicity, precision and economy.¹⁰

5. Mannur Vinodh, et al in the year 2012 had estimated of lacidipine drug by using various analytical methods i.e. HPTLC, LC-MS, UV, LC-PDA and One HPLC method used for determination of lacidipine in biological fluids. For RP-HPLC method i.e. using the mobile phase with gradient system by using the analysis of the drug in pharmaceutical dosage form by using the both qualitative and quantitative analysis in systemic approach required information about purity, quality of drug and concentration of analyte. It performed Acquity UPLC System (Waters Corp., Milford, MA) it consist of a binary solvent and a sample manager, and a photodiode array (PDA) detector isocratic separation with a Waters Acquity BEH C18 column (100 × 2.1mm id, 1.7µm particle size) was used. The mobile phase was 50 mM ammonium acetate–acetic acid buffer (pH of 4.5)–methanol (70:30, v/v). 5µL injection volume and flow rate was 0.25mL/min, column effluent using wavelength at 240nm. duration for 15min.column temperature maintained at 40.c In chromatographic method used to provide the good performance of the assay.i.e used mobile phase like acetonitrile 5mM Ammonium acetate (95:5 v/v) accomplished at 240nm by using an Xbridge C-18 column (150mm x 4.6mm, 5μm). The retention time 8.309 min at a flow-rate of 1.0ml/min was 5µl injection volume used and run time for approx...15min.¹¹

6. Mohd Fazil and Asgar Ali etal in the year 2014 had reported that various different LC analytical methods, used for the application of statistical design along with optimization of mobile phase composition for drugs like for example amoxicillin trihydrate, lenalidomide, voriconazole, risperidone,and fractional factorial design (FFD) and central composite design (CCD) in the screening and optimization of bio analytical methods have been extensively investigated The use of DOE have also been widely explored in metabolite isolation, and impurity profiling using chromatographic procedures. As per prior literature there is no report of an optimized analytical method using experimental design techniques. It was envisaged to develop and validate a simple and fast analytical method by HPLC to quantify LAC in rat plasma by optimization of the mobile phase composition using BBD design. This work describes the validation parameters stated by as per ICH guidelines to achieve the analytical method with acceptable characteristics of suitability, reliability and feasibility.¹²

7. Moorthi et al in the year 2013 to reported that several analytical methods have for the estimation of Lacidipine by LC-DAD (Baranda et al., 2005), UPLC-TMS (Tang et al., 2008), HPTLC (Kharat et al., 2002), HPLC (Ramesh et al., 2009), LC-MS, UV (Nagaraju et al., 2011) and Electrochemical (Juan et al., 1999). However, also to develop a new UV spectrophotometric method used for determination of Lacidipine in pharmaceutical formulations along with good accuracy, simplicity, sensitive, precision, reproducible and economy. Analytical grade methanol, Para Dimethyl Amino Benz aldehyde and Conc.HCL were procured from E-Merck. Shimadzu UV - 1800 UV/VIS spectrophotometer with 1 cm matched quartz cell was used for spectral measurements. Seiko (Japan) DSC model 220°C was used to determine the impurity profiling of Lacidipine and IR spectra were reported using PerkinElmer Paragon 1000 FT-IR spectrophotometer. Methodology used for identification of Functional group of Lacidipine by FT-IR spectrophotometer was utilized to confirm the presence of basic nucleus and functional group of Lacidipine. Impurity profiling of Lacidipine was performed by using Differential scanning colorimetry (DSC). At a scanning rate of 10°C/min. 10mg of drug. Sample was heated and sealed on aluminium pans from 30°C to 400°C to confirm its purity.¹³

8. Sagar Suman Panda1 Et al in the year 2018 to develop a new ultrafast liquid chromatography (UFLC) method used for estimation of lacidipine present in bulk formulation. Further, method validation studies were carried out as per ICH Q2 (R1) guidance. RP-UFLC found for separation tech of lacidipine drug. Mobile phases used higher strengths ammonium acetate as the aqueous phase component. Use of ammonium acetate and other buffers for extensive time tends to plug the C-18 columns due to possible salt precipitation and microbial growth pH of HPLC grade water was maintained at 3.5 using orthophosphoric acid. Lacidipine was separated at 5.1 min and detected by wavelength at 239nm within a run time of 8 min. System suitability such as theoretical plate number and tailing factor were greater than 4200 and less than 1.5, respectively. Establishing a reliable stability-indicating analytical method for lacidipine.¹⁴

9. Maasma Shaikh et al in the year 2019 It reveals that several analytical methods had reported for the estimation of lacidipine by LC-DAD, High Performance Thin Layer Chromatography (HPTLC), LC-MS and UV method. Some HPLC methods were reported in the literature for the determination of lacidipine. To develop a RP - HPLC method, which could be employed for the routine analysis of the drug in pharmaceutical dosage forms using simple mobile phase composition. The present work describes a simple, isocratic RP-HPLC method for the determination of lacidipine tablets as per ICH guidelines¹⁵

10. Juan A. Squella et al in the year 1999 had to reported with the voltammetry oxidation of lacidipine with aqueous–alcoholic solutions (70 + 30) produces a well-defined voltammetric peak when subjected to a differential pulse voltammetric experiment. This peak is due to oxidation of the dihydropyridine ring to a pyridine derivative. This voltammetric response result is irreversible, pH dependent, and diffusion controlled. The best resolution for the peak was obtained at pH 6 in Britton-Robinson buffer–ethanol (70 + 30). The peak potential at pH 6 was 800 mV against an Ag–AgCl reference electrode. A linear relationship between peak current and lacidipine concentration was obtained. For analytical purposes, a calibration curve for lacidipine that covered concentrations between 5 × 10–6 and 2 × 10–4M was used. Detection and quantitation limits were 3.52 × 10–6 and 3.78 × 10–6M, respectively. The repeatability of the measurement was 2%.¹⁶

11. Meenakshi K. Chauhan et al in the year 2014 to reported with the simultaneous estimation of Gliclazide (Gld) and Lacidipine (Ldpn) in combined-dosage form have been described. Techniques used employ 1st order derivative and simultaneous equation method for the simultaneous estimation of the drugs in combination of dosage form. Linearity was observed in the concentration range of 2-20µg/mL for Gld and 4-18 µg/mL for Ldpn. The accuracy of methods was assessed by recovery studies and was found to be within a range of 98-102% for both Gld and Ldpn. The developed methods were validated along with the linearity, accuracy (recovery), and precision. The results were validated statistically as per ICH Q2 R1 guideline and were found to be satisfactory.¹⁷

CONCLUSION:

The literature referred in this article indicates the importance of analytical methods used for the estimation of Lacidipine from bulk and formulations. The spectrophotometric and Chromatographic methods are widely used for the estimation of Lacidipine. In the view of guidelines provided by ICH for the pharmaceuticals it is evident to select HPLC as a method of importance for the estimation of Lacidipine from Bulk and Formulations.

REFERENCES:

1. http://en.wikipedia.org/wiki/Lacidipine

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4. Ramesh G, Vamshi Vishnu Y, Chinna Reddy P, Shravan Kumar Y, Madhusudan Rao Y. Development of High performance liquid chromatography method for Lacidipine in rabbit serum. Anal Chim Acta 2009; 632(2): 278-283

5. Marco Garzotti. Lacidipine, a potential peroxynitrite scavenger investigation of activity by liquid chromatography and mass spectrometry. Rapid Commun Mass Spectrum2003; 17(4): 272-278

6. Jing Tang, Ronghua Zhu, Ruike Zhao, Gang Cheng, Wenxing Peng. Ultra-performance liquid chromatography–tandem mass spectrometry for the determination of Lacidipine in human plasma and its application in a pharmacokinetic study. J Pharm Biomed Anal 2008; 47(4-5): 923-928

7. Arivozhi Mohan, Hitesh B. Patel, Development and Validation of a Reversed-Phase UltraPerformance Liquid Chromatographic Method for Assay of Lacidipine and Related Substances. Journal of AOAC International Vol. 94, no. 6, 2011 (1800-06)

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11. Mannur Vinodh, Mastiholimath Vinayak, Kharya Rahul, Patware Pankaj Development and Validation of A HPLC Method for The Determination of Lacidipine In Pure Form And In Pharmaceutical Dosage Form The Malaysian Journal of Analytical Sciences, Vol 16 No 3 (2012): 213 - 219

12. Mohd Qumbar, Ameeduzzafar, Javed Ali, Syed Sarim Imam, Mohd Fazil and Asgar Ali DOE-Based Stability Indicating RP-HPLC Method for Determination of Lacidipine in Niosomal Gel in Rat: Pharmacokinetic Determination Pharm Anal Acta 2014, 5: 8

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14. Sagar Suman Panda Ravi Kumar Venkata Varaha Bera Sasmita Kumari Acharjya Padmalaya Sahoo Sarwar Beg Analytical life cycle management approach: Application to development of a reliable LC method for estimation of lacidipine Sep Sciplus 2019; 2: 18–25.

15. Maasma Shaik, Dr. Sunandamma, Ch. Srinivasa Reddy, Development and validation of RP-HPLC Assay method for determination of lacidipine in tablets Maasma Shaik et al /J. Pharm. Sci. and Res. Vol. 11(6), 2019, 2204-2207

16. Juan A. Squella, Anny E. Iribarren, Juan C. Sturm, and Luis J. Núñez-vergara, Electrochemical Determination of Lacidipine: Journal of AOAC International VOL. 82, No. 5, 1999

17. Meenakshi K. Chauhan, Parvat K Sahoo, Ashwani Singh Rawat, Arushi Bamrara, Mayank Kandwal and Divya Sharma, Simultaneous estimation of gliclazide and lacidipine using spectrophotometric methods and its application in nanostructured lipid carrier (NLC) development, Der Pharmacia Lettre, 2014, 6 (6): 352-358

Received on 08.03.2021 Modified on 25.04.2021

Asian J. Pharm. Ana. 2021; 11(3):223-226.

DOI: 10.52711/2231-5675.2021.00039