QualityGuidances

GENERAL MATERIAL INFORMATION
General Information	Valsartan film coated tablets is consisting of Valsartan and Excipients.
Categories	Antihypertensive
Composition	Each film coated tablet contains: Valsartan IP………………80 mg &160 mg
Reference	Indian Pharmacopoeia 2022
Sample Quantity	Chemical Analysis = 60 Tablets   Microbiology Analysis = 20 Tablets
Shelf Life	24 Months
Hazards and Precaution, If any	Use nose mask and hand gloves while sampling at bulk stage
Storage	Store protected from moisture at a temperature not exceeding 30°.

 

 

S.NO.	TESTS	SPECIFICATIONS				REFERENCE
1.	Description
2.	Average weight
3.	Uniformity of weight
4.	Identification	A. Shake a quantity of the powdered tablets containing 0.1 g of Valsartan with 40 ml of ethanol, filter and evaporate the filterate to dryness on the residue determine by infrared filtrate to drynes. On the residue, determine by Absorption spectrophotometry (2.4.6). Compare the speetnun with that obtained from valsartan RS or with the reference Spectrum of valsartan. B. In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the Chromatogram obtained with the reference solution.
5.	Hardness	NLT 2.5 kg/cm²
6.	Disintegration Time	NMT 15 min.
7.	Dimension
8.	Friability	NMT 1.0%
9.	Dissolution	NLT 75%
10.	Leak Test	Should be Pass
11.	Related Substance	Determine by liquid chromatography Test solution. Shake a quantity of powdered tablets containing 25 mg of valsartan with 15 ml of mobile phase and dilute to 25.0 ml with the mobile phase, filter. Reference solution  (a) A 0.1 per cent w/v solution of valsartan IPRS in mobile phase Reference solution (b) . Dilute 1.0 ml of reference solution (a) to 100.0 ml with the mobile phase. Chromatographic system as described under assay Inject reference solution (a) the test is not valid unless the tailing factor is not more then 2.0. Inject reference solution (b) and the test solution in the chromatogram obtain with the test solution , the area of any secondary peak is not more the 0.5 time the area of the principa; peak in the chromatogram obtain with reference solution  (b)  ( 0.5 per cent ) and the sum of areasof all the secondary peak is not more than the the area of principal peak in chromatogram obtain with reference solution (b)
12.	Assay:
	Each uncoated tablet contains:		Limit
			Claim	In mg	In %
	Valsartan IP		80 mg	72mg to 88 mg	90% to 110%

SPECIFICATION OF STABILITY ANALYSIS

 

S.NO.	TESTS	SPECIFICATIONS				REFERENCE
1.	Description
2.	Average weight
3.	Uniformity of weight
4.	Identification	A. Shake a quantity of the powdered tablets containing 0.1 g of Valsartan with 40 ml of ethanol, filter and evaporate the filterate to dryness on the residue determine by infrared filtrate to drynes. On the residue, determine by Absorption spectrophotometry (2.4.6). Compare the speetnun with that obtained from valsartan RS or with the reference Spectrum of valsartan. B. In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the Chromatogram obtained with the reference solution.
5.	Hardness	NLT 2.5 kg/cm²
6.	Disintegration Time	NMT 15 min.
7.	Friability	NMT 1.0%
8.	Dissolution	NLT 75%
9.	Related Substance	Determine by liquid chromatolgraphy Test solution. Shake a quantity of powdered tablets containing 25 mg of valsartan with 15 ml of mobile phase and dilute to 25.0 ml with the mobile phase, filter. Reference solution  (a) A 0.1 per cent w/v solution of valsartan IPRS in mobile phase Reference solution  (b) . Dilute 1.0 ml of reference solution  (a) to 100.0 ml with the mobile phase. Chromatographic system as described under assay Inject reference solution (a) the test is not valid unless the tailing factor is not more then 2.0. Inject reference solution (b) and the test solution in the chromatogram obtain with the test solution , the area of any secondary peak is not more the 0.5 time the area of the principa; peak in the chromatogram obtain with reference solution  (b)  ( 0.5 per cent ) and the sum of areasof all the secondary peak is not more then the the area of principal peak in chromatogram obtain with reference solution (b)
10.	Assay:
	Each uncoated tablet contains:		Limit
			Claim	In mg	In %
	Valsartan IP		80 mg

*Related Substance: once in a year.

*Microbial Limit Test: once in a year .

 

 

S.NO.	TESTS	SPECIFICATIONS			REFERENCE
1.	Description
2.	Average weight
3.	Uniformity of weight
4.	Identification	A. Shake a quantity of the powdered tablets containing 0.1 g of Valsartan with 40 ml of ethanol, filter and evaporate the filterate to dryness on the residue determine by infrared filtrate to drynes. On the residue, determine by absorption spectrophotometry (2.4.6). Compare the speetnun with that obtained from valsartan RS or with the reference spectrum of valsartan. B. In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the Chromatogram obtained with the reference solution.
5.	Hardness	NLT
6.	Disintegration Time	NMT
7.	Dimension
8.	Friability	NMT
9.	Dissolution	NLT 70%
10.	Leak Test	Should be Pass
11.	Related Substance	Determine by liquid chromatolgraphy Test solution . Shake a quantity of powdered tablets containing 25 mg of valsartan with 15 ml of mobile phase and dilute to 25.0 ml with the mobile phase, filter . Reference solution  (a) A 0.1 per cent w/v solution of valsartan IPRS in mobile phase Reference solution  (b) . Dilute 1.0 ml of reference solution  (a) to 100.0 ml with the mobile phase. Chromatographic system as described under assay Inject reference solution (a) the test is not valid unless the tailing factor is not more then 2.0. Inject reference solution (b) and the test solution in the chromatogram obtain with the test solution , the area of any secondary peak is not more the 0.5 time the area of the principa; peak in the chromatogram obtain with reference solution  (b)  ( 0.5 per cent ) and the sum of areasof all the secondary peak is not more then the the area of principal peak in chromatogram obtain with reference solution (b)
12.	Assay:
	Each uncoated tablet contains:	Limit
		Claim	In mg	In %
	Valsartan IP	80 mg	72 mg to 88 mg	90% to 110%

 

 

 

SPECIFICATION OF STABILITY ANALYSIS

S.NO.	TESTS	SPECIFICATIONS			REFERENCE
1.	Description
2.	Average weight
3.	Uniformity of weight
4.	Identification	A. Shake a quantity of the powdered tablets containing 0.1 g of Valsartan with 40 ml of ethanol, filter and evaporate the filterate to dryness on the residue determine by infrared filtrate to drynes. On the residue, determine by Absorption spectrophotometry (2.4.6). Compare the speetnun with that obtained from valsartan RS or with the reference Spectrum of valsartan. B. In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the Chromatogram obtained with the reference solution.
5.	Hardness	NLT
6.	Disintegration Time	NMT
7.	Friability	NMT
8.	Dissolution	NLT 70%
9.	Related Substance	Determine by liquid chromatolgraphy Test solution. Shake a quantity of powdered tablets containing 25 mg of valsartan with 15 ml of mobile phase and dilute to 25.0 ml with the mobile phase, filter. Reference solution  (a) A 0.1 per cent w/v solution of valsartan IPRS in mobile phase Reference solution  (b) . Dilute 1.0 ml of reference solution  (a) to 100.0 ml with the mobile phase. Chromatographic system as described under assay Inject reference solution (a) the test is not valid unless the tailing factor is not more then 2.0. Inject reference solution (b) and the test solution in the chromatogram obtain with the test solution , the area of any secondary peak is not more the 0.5 time the area of the principa; peak in the chromatogram obtain with reference solution  (b)  ( 0.5 per cent ) and the sum of areasof all the secondary peak is not more then the the area of principal peak in chromatogram obtain with reference solution (b)
10.	Assay:
	Each uncoated tablet contains:	Limit
		Claim	In mg	In %
	Valsartan IP	80 mg	72 mg to 88mg

 

*Related Substance: once in a year.

*Microbial Limit Test: once in a year.

 

STANDARD TESTING PROCEDURE

• Description: Visual

 Average Weight: Check weight of 20 tablets at randomly and calculate the average weight by formula.

Average weight (mg) =   wt of 20 tablets (gm) x 1000

20

• Uniformity of weight:

Weigh 20 tablets selected at random and calculate the average weight. Not more than two of the individual weights deviate from the average weight by more than the percentage shown in table.

Tablets were weighed individually and the percentage of deviation of its weight from the average weight was determined for each tablet. Formula to calculate the percentage of deviation.

Deviation (%) = Weight of each tablet – Average weight    x 100

Average weight

Average weight of tablets	Percentage deviation
More than 80mg but Less than 250mg	±7.5%

 Identification Test: A. Shake a quantity of the powdered tablets containing 0.1 g of Valsartan with 40 ml of ethanol, filter and evaporate the filterate to dryness on the residue determine by infrared filtrate to drynes. On the residue, determine by absorption spectrophotometry (2.4.6). Compare the speetnun with that obtained from valsartan RS or with the reference

Spectrum of valsartan. B. In the Assay, the principal peak in the chromatogram

obtained with the test solution corresponds to the peak in the chromatogram obtained with the     reference solution.

5.0)     Hardness:

The standard method used for tablet hardness testing is compression testing. The tablet is placed between two jaws that crush the tablet. The machine measures the force applied to the tablet and detects when it fractures.

6.0)     Disintegration Time: 

Unless otherwise stated in the individual monograph, introduce one tablet into each tube and add a disc to each tube. The assembly is suspended in the liquid medium in a suitable vessel, preferably a 1-litre beaker. The volume of liquid is such that the wire mesh at its highest point is at least 15mm below the surface of the liquid, and at its lower point is at least 25mm above the bottom of the beaker. At no time should the top of the basket-rack assembly become submerged. There is a thermostatic arrangement for heating the liquid and maintaining the temperature at 37±2°.

If 1 or 2 tablets fail to disintegrate, repeat the test on 12 additional tablets; not less than 16 of the total of 18 tablets tested disintegrate.

If the tablets adhere to the disc and the preparation under examination fails to comply, repeat the test omitting the disc. The preparation complies with the test if all the tablets in the repeat test disintegrate.

7.0)     Dimension of Tablet:

Diameter and thickness are determined by vernier calliper in mm.

8.0)      Friability:

The test is applicable to compressed tablets and is intended to determine the physical strength of tablets. Tablets with a unit weight equal to or less than 650 mg, take a sample of whole tablets corresponding as near as possible to 6.5 g. For tablets with a unit weight of more than 650mg, take a sample of 10 whole tablets. The tablets should be carefully dedusted prior to testing. Accurately weigh the tablet sample, and place the tablets in the drum. Rotate the drum 100 times and remove the tablets. Remove any loose dust from the tablets as before, and accurately weigh.

The test is run only once unless the results are difficult to interpret or if the weight loss is greater than the target value, in which case, the test is repeated twice and the mean of the three tests is determined.

% Friability =                 W₁ – W₂ X 100

                                                      W₁

W₁= Initial weight                  W₂= Final weight

            A maximum loss of weight (From a single test or from the mean of three tests) not greater than 1.0 percent is acceptable for most tablets.

If obviously cracked, chipped or broken tablets are present in the sample after tumbling, the sample fails the test.

9.0)      Dissolution:

                Apparatus No. 1,

Medium. 900 ml of phosphate buffer pH 6.8,

Speed and time. 50 rpm and 45 minutes.

Withdraw a suitable volume of the medium and filter. Measure the absorbance of the filtered solution, suitably diluted with the medium if necessary, at the maximum at about 250 nm. Calculate the content of Valsartan in the medium from the absorbance obtained from a solution of known

Concentration of valsartan RS prepared by dissolving in minimum amount of methanol and diluted with the dissolution

Medium.

1. Not less than 70 per cent of the stated amount of Valsartan

 10.0)   Leak test:

The apparatus is used to test for the integrity of packed strips, blisters and Alu-Alu Blister pack containing tablets. Ensure apparatus bath is filled with purified water upto mark indicated and add 0.5% crystal violet solution in water. Samples are placed into the desiccators and the lid is placed in position. The pump starts to produce a vacuum 15inHg inside the desiccators and the vacuum is held for 1 minute. The sample remains at the required vacuum level for given time interval buzzer will sound after time is over and will cut off the vacuum pump. As the package is immersed in a colored dye solution the venting of the desiccators will allow any holes to be penetrated by the dye and the contents of the flexible packaging will also be stained with the same coloring material.

Examine all the strips for any leakage by opening the pockets manually. If anyone pocket shows evidence of leakage, reject the sample, stop the Blister / Strip machine and immediately take corrective action.

11.0)    Related Substance:

Determine by liquid chromatolgraphy

Test solution . Shake a quantity of powdered tablets containing 25 mg of valsartan with 15 ml of mobile phase and dilute to 25.0 ml with the mobile phase, filter .

Reference solution  (a) A 0.1 per cent w/v solution of valsartan IPRS in mobile phase

Reference solution  (b) . Dilute 1.0 ml of reference solution  (a) to 100.0 ml with the mobile phase.

Chromatographic system as described under assay

Inject reference solution (a) the test is not valid unless the tailing factor is not more then 2.0.

Inject reference solution (b) and the test solution in the chromatogram obtain with the test solution , the area of any secondary peak is not more the 0.5 time the area of the principa; peak in the chromatogram obtain with reference solution  (b)  ( 0.5 per cent ) and the sum of areasof all the secondary peak is not more then the the area of principal peak in chromatogram obtain with reference solution (b)

12.0)   Assay: . Determine by liquid chromatography

Test solution. Weigh and powder 20 tablets. Disperse a quantity of powder containing 50 mg of Valsartan in 25 ml of the mobile phase and dilute to 100.0 ml with the mobile phase and filter. Dilute 5.0 ml of this solution to 50.0 ml with the mobile phase.

Reference  solution. A 0.005 per cent w/v solution of  valsartan IPRS in the mobile phase.

Chromatographic system

 

-A stainless steel column of  25 cm x 4.6 mm, packed with octadesylsilane bonded to porous silica

(5 µm),

– mobile phase: a mixture of 50 volumes of water, 50

-volumes of acetonitrile and 0.1 volume of glacial acetic acid.

-flow rate: 1 ml per minute,

-spectrophotometer set at 273 nm,

– injection volume: 10 µm

Inject the reference solution. The test is not valid unless the tailing factor is not more than 2.0 and the relative standard deviation for replicate injections is not more than 2.0 per cent.

Inject the reference solution and the test solution.

Calculate the content of C₂₄H ₂₉N₅0₃ in the tablets.

 

Acceptance criteria: 90.0%-110.0%

 

            Abbreviations:

Wt.: Weight

ml: Millilitre

inHg: Inch of Mercury

O.P.A: Orthophosphoric acid

G.A.A: Glacial acetic acid

mg: Milligram

STD: Standard

rpm: Rotations per minute

NaOH: Sodium Hydroxide

HCl: Hydrochloric acid