UV Spectroscopy Analysis and Degradation Study of Irbesartan

 

Vishal V. Bilaskar*, Indrajeet S. Patil, Omkar A. Patil, Dr. Srinivas K. Mohite

Department of Pharmaceutics, Rajarambapu College of Pharmacy, Kasegaon, Maharashtra India- 415404

*Corresponding Author E-mail: vishalbilaskar92@gmail.com

 

ABSTRACT:

Irbesartan is an antihypertensive drug, undergoes hepatic first pass metabolism and low oral bioavailability. According to ICH guidelines factors which cause forced degradation of a drug product comprise of temperature, time, photo degradation, pH variation (high and low), acid/base Stress testing and/ or with humidity. UV-Vi spectroscopy method was designed to examine and calculate the quantity of drug in the presence of degradation products. According to the WHO, the official assay limit of the content should not less than 99%and not more than 101% of labelled amount of Irbesartan. From our experiment we can conclude that Irbesartan degrades most when exposed to UV light and heat but do not degrades in basic medium whereas slight degradation occurs in acidic medium.

 

KEYWORDS: Irbesartan, Degradation, UV.

 

 


INTRODUCTION:

Irbesartan is an orally active specific angiotensin II receptor antagonist used, as a hypotensive agent and does not require biotransformation into an active form. Chemically it is 2-butyl-3-[p-(o-1H-tetrazol-5-ylphenyl) benzyl]-1, 3-diazaspiro [4.4] non-1-en-4-one 1. Its empirical formula is C25H28N6O. Irbesartan is a white to off white crystalline powder with a molecular weight of 428.5. Irbesartan is slightly soluble in alcohol and methylene chloride and practically insoluble in water2

 

 

 

It may also delay progression of diabetic nephropathy and also indicated for the reduction of renal disease progression in patients with type 2 diabetes, hypertension and micro albuminria or proteinuria. Irbesartan, a widely prescribed anti hypertensive drug belongs to class II under BCS classification and exhibit low and variable oral bioavailability due to its poor aqueous solubility3,4.

 

Irbesartan inhibits the activity of angiotensin II (AII) via specific, selective non-competitive antagonism of the AII receptor subtype 1 (AT1) which mediates most of the known physiological activities of AII5. It has the oral bioavailability of 60-80% and the half life of the drug is 11-15hours6. Irbesartan is a non-peptide tetrazole derivative and an angiotensinII antagonist which blocks the binding of angiotensin-II to the angiotensin-II AT1-receptor. Angiotensin II stimulates the adrenal cortex to synthesize and secrete aldosterone, which ultimately decreases the excretion of sodium and increases the excretion of potassium. Angiotensin-II also acts as a vasoconstrictor in vascular smooth muscle. Irbesartan, by blocking the binding of angiotensin-II to the AT1 receptor, promotes vasodilatation and decreases the eects of aldosterone and thus lower the blood pressure7’8. Stability testing of new drug substances and drug products requires a stress testing, which should be carried out to elucidate the inherent stability characteristics of the active substance. It suggests that the degradation products, which were formed under variety of conditions, Should be identified and degradation pathways are to be established9.

 

 

Figure 1: Chemical Structure of Irbesartan.

 

Spectrophotometry is usually prefer over other methods because of less equipment cost and economical maintenance advantage. Spectrophotometric technique is based on measuring the   absorption of a monochromatic light in the near ultraviolet region (200- 380 nm) by colorless complex10. The aim of the present work was to develop an accurate, specific, reproducible, and stability indicating method for the determination of Irbesartan in the presence of its degradation products and related impurities as per ICH guideline.11

 

MATERIALS AND METHODS:

Parameters Involve in Forced Degradation:

The distinctive forced degradation studies on drug substance involve acid/base stress testing, photo degradation, temperature, time, pH variation (low and high).

 

Acid/Base Stress Testing:

Acid/base stress testing is used for the evaluation of forced degradation of a drug substance. This test involves degradation of a drug substance by exposure to basic or acidic medium over time to its primary degradation products. In carbonyl functional group like alcohol, imines, imides, amides, esters (lactones) aryl amines, carbomets acid and base degradation take place by hydrolysis.

 

Degradation by UV light:

Many formulation or products made of synthetic or natural polymer are UV unstable. They degrade or disintegrate expose to continuous sunlight. The degree of disintegration is depends up on degree of exsposer.

 

 

 

 

 

Thermal (Heat) and / or humidity stress testing:

Many drugs are thermal (heat) and humidity sensitive. Thermal (Heat) and humidity is degrade substance up to its main components. This test is performed by exposing the drug or formulation to thermal / humidity condition.

 

EXPERIMENTAL:

Material and Reagents:

Irbesartan:

We take active Irbesartan for purpose of degradation study.

 

Instruments:

UV- visible spectrophotometer (JASCO V-630) with quartz cuvett,Weighing balance,Constant temperature water bath.

 

Reagents:

All reagents are analytical grade were used. Which include sodium hydroxide (NaOH), Hydrochloric acid (HCL) and distilled water.                                                      

 

Preparation of solution:

Following methods was to preparation of 0.1N NaOH and Irbesartan solution.

 

Preparation of 0.1 N Hydrochloric acid solution:-   0.1 N hydrochloric acid was prepared by taking 8.3 ml hydrochloric acid (HCl) in 100 ml volumetric flask having purity 37% and make up the final volume up to the mark of the flask with distilled water.

 

Preparation of 0.1 N sodium hydroxide solution:

0.1N sodium hydroxide solution prepared by accurately weighing 4 gm of sodium hydroxide (NaOH) and transfers it into 100ml of volumetric flask. Add small amount of water to dissolve NaOH and make up final volume up to the mark of flask with distilled water.

 

Preparation of Irbesartan:

200ppm Irbesartan solution prepared by accurately weighing 0.020gm active Irbesartan and transfers it into 100ml volumetric flask. Add small amount of water in volumetric flask to dissolve Irbesartan and finally make volume up to mark with distilled water. The absorbance of prepared solution of Irbesartan was measured by UV spectrophotometer at maximum wavelength 244 nm.

 

Procedure for degradation studies:

For acid:

To study degradation in acid medium or to determine effect of acid on Irbesartan. Take 5ml of 200ppm Irbesartan solution and add 5ml of 0.1 N hydrochloric acid (HCL) solution and left it for 30 minutes. After 30 minutes absorbance of solution was measured by UV spectrophotometer at maximum wavelength 244nm.

 

For base:

To study degradation in basic medium or to determine effect of base on Irbesartan take 5ml of 200ppm Irbesartan solution in the test tube and add5ml of 0.1 N sodium hydroxide solution  (NaOH) left it is for 30 minutes .After 30 minutes absorbance of solution was measured by UV spectrophotometer at maximum wavelength 244nm.

 

For UV light:

To study degradation in UV light medium or to determine effect of UV light on Irbesartan take 5ml of 200ppm Irbesartan solution in test tube and add 5ml distilled water left it for 30 minutes in UV light of 320nm. After 30 minutes absorbance of solution was measured by UV spectrophotometer at 244 nm.

 

For thermal (Heat):

To study degradation in thermal medium or to determine effect of heat on Irbesartan. Take 5ml of 200ppm Irbesartan solution and add 5ml of distilled water left it for 30 minutes in water bath at 50 c. After 30 minutes absorbance of solution was measured by UV spectrophotometer at maximum wavelength 244 nm.

 

RESULT AND DISCUSSION:

Degradation studies are an essential step in the development of new drug product.  Many factors are responsible for degradation of drug or product like temperature humidity, and light .In this research work we studies effect of various factor like acid, base, UV light and heat on drug (Irbesartan).

 

For Irbesartan, absorbance of various parameters given in Table 1and in Figure 1 and Degradation Pattern in Percentage given in Table 2 and in Figure 2.

 

When Irbesartan subjected to 0.1N HCL, Irbesartan do not showed significant changes in terms of availability (99.12%). In the same way Irbesartan subjected to 0.1 N NaOH Irbesartan showed highly significant change in term of availability (124.02%). When Irbesartan exposed to heat for 30 minutes, highly decreased availability observed (81.08%) and when exposed to U.V light, Irbesartan also showed decreased availability (97.39%).

But From our results we can conclude that Irbesartan do not degrade when introduced in acidic medium i.e. 0.1N HCl. (99.12 %). but degrades to larger extend when subjected to basic medium i.e. 0.1N NaOH i.e. 124.02%. When Irbesartan exposed to UV light (244 nm) and heat for 30 minutes high degradation was observed i.e. 81.08. % and 97.39% respectively.

 

 

 

Figure 2: Absorbance of Irbesartan

 

 

Figure 3: Degradation Pattern of Irbesartan

 

Table1: Absorbance of Irbesartan.

Degradation

Parameters

Irbesartan

1

2

3

Average

Before

1.7995

1.7990

1.7992

1.7992

After acid

1.7832

1.7834

1.7840

1.7835

After base

2.2315

2.2317

2.2315

2.2315

After heat

1.4589

1.4592

1.4586

1.4589

After U.V

1.7523

1.7524

1.7527

1.7524

 

 

Table2: Degradation Pattern in Percentage of Irbesartan

Degradation

Parameters

Irbesartan

1

2

3

Average

Before

100.01

99.98

100

99.99

After acid

99.11

99.12

99.15

99.12

After base

124.02

124.03

124.02

124.02

After heat

81.08

81.10

81.06

81.08

After U.V

97.39

97.39

97.41

97.39

 

 

 

 

 

 

CONCLUSION:

According to specification given in WHO monographic for Irbesartan, the official assay limit of the content should not less than 99% and not more than 101% of the estimated potency.  From our result we concluded that Irbesartan degrades to a very larger extend when exposed to basic medium whereas it also degrades in the presence of acidic medium, heat and UV light.

 

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Received on 06.02.2018       Accepted on 21.04.2018     

© Asian Pharma Press All Right Reserved

Asian J. Pharm. Ana. 2018; 8(2): 69-72.

DOI: 10.5958/2231-5675.2018.00013.3