INTRODUCTION:

Depression is one of the chronic, recurrent, and probably life-threatening disease that affects up to about 20% of the global population.^1-2 Depression is an immoderate general and impairing disease with an important social and economic outcome, most of the antidepressant agents are to be useful in the management of disorder, there are the some of the limitations of efficacy, because of various types of side effects can be experienced. Some of the harmful effects found to be risk for the life threating arrhythmias, mostly in patients with early survive cardiac disease or after overdose direction.³

Venlafaxine is one of the new generation antidepressant, and it is usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI) and the drug is showing effective anti-depressant properties, but it has been referred to as a serotonin-norepinephrine dopamine reuptake inhibitor, introduced by Wyeth in 1993.^4-6 Venlafaxine HCl is an orally active serotonin noradrenalin reuptake inhibitor which is used for the treatment of major depressive disorders. The successful treatment of depression mostly depends on the management of effective drug concentration level in the body for which a constant and uniform supply of the drug is required.⁷ Venlafaxine affects on chemical messengers like neurotransmitters, serotonin, dopamine, and norepinephrine in the brain. Venlafaxine act by inhibiting the release or affecting the action of these neurotransmitters.⁸

Table No.1: Drug Profile of Venlaflaxine HCl

Drug name	Venlafaxine HCl
Category	Anti-depressant
Chemical Formula	C₁₇H₂₈ClNO₂
IUPAC Name	1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexane-1-ol
Molecular weight	277.402 g/mol
Melting point	215-217⁰C
Solubility	Freely soluble: Water, Methanol
BCS Class	Class-I[High Solubility and High Permeability]
Half life	5 hours

Fig.No.1. Chemical structure of Venlafaxine HCl

Analytical Methods Used for Determination of Venlafaxine HCl

1. High Performance Liquid Chromatography (HPLC):

High Performance Liquid Chromatography is mainly a term that is typically accustomed describes the liquid chromatography which consists of the liquid mobile phase that is pumped mechanically through a column that contains the stationary phase. An HPLC includes the an injector, a pump, a column and lastly the detector.⁹ The pump controls the succession of solvent through the system. Upon leaving the pump, then the solvent enters the injector, at that time it then goes through the section so last through the optical unit of a detector.¹⁰

Table No.2: Summary of RP-HPLC method for determination of Venlafaxine HCl

Sr. No	Drug	Method	Description	Reference
1.	Venlafaxine HCl	RP-HPLC	Column: ODS-C18 Mobile phase: Acetonitrile: Sodium acetate (65:35 v/v) Flow rate: 1ml/min Retention time: 2.83 min	11
2.	Venlafaxine HCl	RP-HPLC	Column: Microsorb MV 100 C18 Mobile phase: Acetonitrile:0.04M potassium dihydrogen phosphate: Methanol (45:25:30 v/v) Flow rate: 1ml/min Retention time: 3.43 min	12
3.	Venlafaxine HCl	RP-HPLC	Column: Kromasil KR 100-5 C18 Mobile phase: Diethylamine: Methanol (90:10 v/v) Flow rate: 1ml/min Retention time: 5 min	13
4.	Venlafaxine HCl, Modafinil	RP-HPLC	Column: C18 Mobile phase: Ammonium acetate buffer: 10% Methanol in acetonitrile (60:40) Flow rate: 1ml/min Retention time: Venlafaxine HCl: 4.4min Modafinil: 6.4min	14
5.	Venlafaxine HCl	HPLC	Column: C18 Mobile phase: Acetonitrile: Potassium phosphate buffer (30:20 v/v) Flow rate: 1ml/min Retention time: 15.2 min	15
6.	Venlafaxine HCL	HPLC	Column: C18 Mobile phase: Acetonitrile: phosphate buffer (22:78 v/v) Flow rate: 1.0ml/min	16
7.	Venlafaxine HCL	HPLC	Column: ODS RP-C18 Mobile phase: Acetonitrile: water (70:30 v/v) Flow rate: 1.5ml/min Retention rate: 4.8min	17
8.	Venlafaxine HCL	RP-HPLC	Column: Phenomenex Gemini C18 Mobile phase: Methanol: 0.05M Potassium dihydrogen orthophosphate (70:30 v/v) Flow rate: 1ml/min Retention time: 3.7min	18

2. UV Spectroscopy Method:

The main principle behind the UV Spectroscopy is that the absorption of visible and ultraviolet radiation i.e within the 200-400nm is related to the excitation of electrons, in each atoms and molecules, from lower to higher energy levels.¹⁹ The Beer-Lambert law gives the statement that the absorbance of a solution is directly proportional to the concentration of the absorbing species in the solution and that of the path length.²⁰

Principle:

A molecule or particle can exhibit absorption within the visible or ultraviolet region once the radiation causes an electronic transition inside its structure. Thus, the absorption of light by a sample within the ultraviolet or visible region is attended by a change in the electronic state of the molecules within the sample. The energy provided by the light can promote electrons from their ground state orbitals to the higher energy, excited state orbitals.²¹

Instrument needed for measurement of the UV or visible radiations mainly consists of the source i.e is supplier of light, wavelength selector, sample containers, detector, signal processor and readout device. Source mainly contains the hydrogen lamps, tungsten, deuterium lamps and halogen lamps. The wavelength selector consists of an entrance slit, a collimating lens, a dispersing device, a focusing lens and an exit slit. The container for the sample and reference solution should be transparent to the radiation. Mostly the quartz cuvettes are used. The photomultiplier tube is often used as a detector in UV-Visible spectroscopy and other different detector used are the linear photodiode array and Charge-Coupled Devices (CCDs).²²

Table No.3: Summary of UV Spectroscopic methods for determination of Venlafaxine HCl

Sr. No	Drug	Method	Description	Reference
1.	Venlafaxine HCL	UV-Spectrophotometric Method	Wavelength:224nm Solvent: Water Linearity:2-14ug/ml	23
2.	Venlafaxine HCL	UV-Spectrophotometric Method	Wavelength:225nm Solvent:Water Linearity:2-24ug/ml	24
3.	Venlafaxine HCL	UV-Visible Spectrophotometric method	Wavelength:222nm Solvent: Phosphate buffer Linearity:2-26ug/ml	25
4.	Venlafaxine HCL	UV-Visible Spectrophotometric Method	Wavelength:225.20nm Solvent: Water Linearity:4-20ug/ml	26
5.	Venlafaxine HCL	UV-Spectrophotometric Method	Wavelength:274nm Solvent:0.1N HCL Linearity:10-250ug/ml	27
6.	Venlafaxine HCL	UV-Visible Spectrophotometric Method	Wavelength:223nm Solvent:0.1N NaOH Linearity:5-25ug/ml	28
7.	Venlafaxine HCL	UV-Spectrophotometric Method	Wavelength:225.27nm Solvent: Water Linearity:4-24ug/ml	29
8.	Venlafaxine HCL	UV-Visible Spectrophotometric Method	Wavelength:227nm Solvent: Water and Methanol(50:50) Linearity:4-70ug/ml	30
9.	Venlafaxine HCL, Bupropion HCL	UV-Spectrophotometric Method	Wavelength: For Venlafaxine HCL:223nm For Bupropion HCL:249nm Solvent: Methanol and Water Linearity:4-24ug/ml	31

3. High Performance Thin Layer Chromatography:

HPTLC is one amongst the advanced type of Thin Layer Chromatography. It satisfies all quality requirements/necessities which are required for today’s analytical labs, mainly to reinforce the resolution and to permit accurate quantitative measurements.³² HPTLC plates furnish improved resolution, higher detection sensitivity, and improved in situ quantification and which are largely used for industrial pharmaceutical densitometric quantitative analysis.³³ The HPTLC framework (Camag, Muttenz, Switzerland) outfit with an associate example implement Linomat-V related with the nitrogen chamber, twin trough plate advancement chamber (10×10cm), TLC Camag Scanner III and Wincats-4.02 pre-covered silica gel 60 F254 TLC aluminum plates.³⁴

Table No.4: Summary of HPTLC method for determination of Venlafaxine HCl

Sr. No

Drug

Method

Description

Reference

Venlafaxine HCL

HPTLC

Linearity:500-3000ug/ml

Solvent: Methanol and Ammonia (4.5:0.5v/v)

Wavelength:224nm

Plate development time:20 min

Venlafaxine HCL

HPTLC

Linearity:400-2000ug/ml

Solvent: Toluene and Methanol (7:3.5v/v)

Wavelength:228nm

Plate development time:20 min

4. Stability Indicating Method:

The main reason to carry out the stability studies is mainly for the concern of the human beings which have the particular disease and for which a particular product is intended to be used. In this method the stability studies of the drug in basic, acidic, oxidative, photolytic and thermal degradation is carried out. Stability studies conjointly provides the knowledge for the selection of the excipients, formulation, container closure system for the development of new product, for storage condition for development of a new product and to determine shelf life.^36-39

Table No.5: Summary of Stability Indicating methods for determination of Venlafaxine HCl

Sr. No	Drug	Method	Description	Reference
1.	Venlafaxine HCL	RP-HPLC	Column: Agilent C18 column Mobile phase: Methanol and Phosphate buffer (60:40% v/v) Flow rate:1 ml/min Wavelength:235 nm	40
2.	Venlafaxine HCL	HPLC	Column: RP inertsil ODS-3V C18 column Mobile phase: Phosphate buffer and Acetonitrile (80:20) Flow rate:0.8ml/min Wavelength:225nm	41
3.	Venlafaxine HCL	LC	Column: Spherisorb C8 column Mobile phase: Acetonitrile and Sodium Dihydrogen orthophosphate (75:25) Flow rate:1.5ml/min Wavelength:224 nm	42

CONCLUSION:

So, from the above information it should be concluded that the various analytical methods which were used for the determination of Venlafaxine HCl alone or in combination has been successfully used on a routine basis and allows the quantification of the drug in various pharmaceutical dosage forms. These all methods are simple, fast, accurate, sensitive, reproducible and possess excellent linearity and precision characteristic.

ACKNOWLEDGMENT:

I would like to express my sincere thanks to Dr. Suhas Siddheshwar and Prof. Ganesh Shinde for their valuable guidance and support for this review work.

REFERENCE:

1. Misra R, Bhardwaj P. Hindawi Publishing Corporation, Scientifica, 2016, 1-13.

2. Berton O, Nestler EJ. New approaches to antidepressant drug discovery: beyond monoamines. Nature Reviews Neuroscience, 2006,1;7(2):137-151.

3. Khalifa M, Daleau P, Turgeon J. Mechanism of sodium channel block by venlafaxine in guinea pig ventricular myocytes. Journal of Pharmacology and Experimental Therapeutics, 1999; 1(4): 280-291.

4. Baldania SL, Bhatt KK, Mehta RS. Indian Journal of Pharmaceutical Sciences, 70(1), 124–128.

5. Momin MM, Kane S, Abhang P. Formulation and evaluation of bilayer tablet for bimodal release of venlafaxine hydrochloride. Frontiers in pharmacology, 2015; 6.

6. Krishna KV, Satyavathi K, Venu M. Design and Evaluation of Extended release tablet of Venlafaxine Hydrochloride using Compression coating method. International Journal of Scientific and Research Publications, 2014; 610.

7. Patil P, Rashmi, Prashant P, Viraj S. International Journal of Pharmacy and Pharmaceutical Sciences, 2013; 5, 757-765.

8. Edla S. A Novel RP-HPLC method for the determination of Venlafaxine in pharmaceutical drug products. International journal of Science and Technology, 2012; 1(1): 11-21.

9. Andrea Weston and Phyllis R. Brown, HPLC and CE Principles and Practice, academic press, 1997, 01.

10. Siddiqui MR, Alothman ZA, Rahman N. Analytical techniques in pharmaceutical analysis: A review. Arabian Journal of chemistry, 2017, 1;10: 1409-1421.

11. Kiran BV, Rao BS, Som Shankar Dubey. Validation of Venlafaxine in Pharmaceutical Dosage by Reverse Phase HPLC Method. Journal of Pharmacy Research, 2012; 5(5): 2683-2700.

12. Somasekhar V, Gowrisankar D, Shivakumar HN. Development and validation of a rapid RP-HPLC method for the determination of venlafaxine hydrochloride in pharmaceutical dosage forms using experimental design. Journal of Chemistry, 2009; 6(4): 1091-1102.

13. Nageswara RR, Narasa RA. Simultaneous separation and determination of process‐related substances and degradation products of venlafaxine by reversed‐phase HPLC. Journal of Separation Science, 2006; 29(18): 2733-2744.

14. Younus M, Arif MF, Richards MP, Kumar B. Determination of venlafaxine and modafinil in individual tablet dosage forms using single RP-HPLC method. Tropical Journal of Pharmaceutical Research, 2013;12(2): 239-245.

15. Asafu-Adjaye EB, Faustino PJ, Tawakkul MA, Anderson LW, Lawrence XY, Kwon H, Volpe DA. Validation and application of a stability-indicating HPLC method for the in vitro determination of gastric and intestinal stability of venlafaxine. Journal of Pharmaceutical and Biomedical Analysis, 2007, 11;43(5): 1854-1890.

16. Georgi B, Snezha Z, Petko M, Ivelina S, Ivaylo V. A simple method for quantitative determination of venlafaxine in blood by high-performance liquid chromatography. International Journal of Chemical Studies, 2018; 6(4): 801-804.

17. Peikova L, Ivanka P, and Vanita M. Development of HPLC method for determination of Venlafaxine during concomitant use of metoprolol. Pharmacia 60 (2013): 12-16.

18. Baldania SL, Bhatt KK, Mehta RS, Shah DA and Gandhi TR. RP-HPLC Estimation of Venlafaxine Hydrochloride in Tablet Dosage Forms. Indian Journal of Pharmaceutical Sciences, 2008, 70 (1): 124-128.

19. Pavia D, Lampman G, Krix G. Introduction to Spectroscopy. Bloomington, IN: Indiana University, 2001.

20. Gandhimathi R, Vijayaraj S, Jyothirmaie MP. A Review: Analytical process of drugs by Ultraviolet Spectroscopy. International Journal of Institutional Pharmacy and Life Sciences, 2015, 5(5): 490-505.

21. Basic UV-Vis Theory, Concepts and Applications, 7-10.

22. Sheffield Hallam University, UV-Visible Spectroscopy Instrumentation, 2015.

23. Sundaraganapathy R, Jambulingam M, Ananda TS, Subasini U. Development and Validation of UV Spectrophotometric Method for the Determination of Venlafaxine Hydrochloride in Bulk and Solid dosage forms. International Journal of Pharmacy and Industrial Research, 2011; 1(1): 28-31.

24. Eswarudu MM, Anitha V, Srinivasa PB. New Simple UV Spectrophotometric Method for determination of Venlafaxine Hydrochloride in pure and pharmaceutical formulation. World Journal of Pharmacy and Pharmaceutical Sciences, 2017, 6(7): 1292-1300.

25. Sowmya C, Reddy YP, Kumar MK, Santhosh MR. Development and Validation of Spectrophotometric Method for the estimation of Venlafaxine in bulk and formulation. International Journal of Chemical Science, 2011,9(1): 52-58.

26. Bansode AS, Saravanan K. Analytical Method Development and Estimation of Venlafaxine Hydrochloride in Bulk and Pharmaceutical Dosage Form by UV- Visible Spectrophotometer. International Journal of Innovative Science, Engineering and Technology, 2019,6(10): 131-138.

27. Lavanya K, Sunita P, Anil KA, Venkata RK, New Simple UV Spectrophotometric Method for determination of venlafaxine hydrochloride in bulk and pharmaceutical dosage forms. International Journal of Pharmaceutical Quality Assurance, 2013, 4(1): 1-3.

28. Pakhale BA, Shinkar DM, Saudagar RB. Development and Validation of Spectrophotometric method for determination of venlafaxine hydrochloride. International Journal of Pharma Sciences and Research, 2015, 6(1): 66-69.

29. Nikhil AK, Prashant P. Analytical method development and validation of venlafaxine hydrochloride in solid dosage forms using UV spectrophotometer. Journal of Pharmacy Research, 2009, 2(7): 1246-1249.

30. Dhiraj K, Jitendra D, Priyanka Y, Arjun G. Method development and estimation of Venlafaxine Hydrochloride in bulk and Pharmaceutical dosage forms using UV-VIS. International Journal of Drug Development and Research, 2013, 5(4): 133-139.

31. Shubham MJ, Zaranappa. Development and Validation of UV – Spectrophotometric Method for Simultaneous Estimation of Venlafaxine Hydrochloride and Bupropion Hydrochloride in Bulk and Pharmaceutical Dosage Forms. International Journal of Pharmacy and Pharmaceutical Research, 2019; 16(4): 438-451.

32. Patel RB, Patel MR, Patel BG (2011). Experimental Aspects and Implementation of HPTLC. In: Shrivastava, M.M. HPTLC. New York: Springer, 41- 54.

33. Shrivastava MM. An Overview of HPTLC: A Modern Analytical Technique with Excellent Potential for Automation, Optimization, Hyphenation, and Multidimensional Applications. In: Shrivastava, M.M. HPTLC. New York: Springer, 2011, 3- 24.

34. Redasani VK, Patel PR, Surana SJ. Development and Validation of Venlafaxine Hydrochloride in Bulk and in Capsule Formulation by HPTLC. Journal Analytical and Pharmaceutical Research, 2017, 4(3): 00103.

35. Shirvi V, Channabasavaraj K, Kumar G, Mani T. HPTLC analysis of venlafaxine hydrochloride in the bulk drug and tablets. Journal of Planar Chromatography-Modern TLC, 2010, 23(5): 369-372.

36. Singh S, Bakshi M. Guidance on conduct of stress test to determine inherent stability of drugs. Pharm Technol Asia, 2000, 24-36.

37. Kommanaboyina B, Rhodes CT. Trends in stability testing with Emphasis on Stability during Distribution and Storage. Drug Development and Industrial Pharmacy, 1999, 25: 857-867.

38. Singh S. Stability testing during product development in Jain NK Pharmaceutical product development, CBS publisher and distributors, India, 2000, 272-293.

39. Carstensen JT. Drug Stability, Principles and Practices, Marcel Dekker, New York, 2000.

40. Ajitha A, Rani GS. Stability Indicating RP-HPLC Method Development and Validation for determination of related substance in Venlafaxine Hydrochloride Tablet. International Journal of Pharmaceutical Sciences and Research, 2020; 11(8): 3923-3929.

41. Srinivas CS, Devi RP, Gampa V. Stability indicating method of related impurities in venlafaxine hydrochloride sustained release tablets. International Journal of Advanced Pharmaceutical Sciences, 2010;1(2):177-183.

42. Makhija SN, Vavia PR. Stability indicating LC method for the estimation of venlafaxine in Pharmaceutical Formulations. Journal of pharmaceutical and biomedical analysis, 2002; 28(6):1055-1090.

Received on 27.04.2021 Modified on 16.05.2021

Research J. Science and Tech. 2021; 13(3):208-212.

DOI: 10.52711/2349-2988.2021.00032