Vonoprazan Fumarate is a medication used to treat gastroesophageal reflux disease (GERD) and other gastrointestinal disorders. The SOP for Vonoprazan 10 mg Tablet Testing Procedure should follow the appropriate regulatory guidelines and be validated to ensure the accuracy, precision, and reliability of the results.
PURPOSE:
To describe the procedure for analysis at in-process and finished stage of Vonoprazan 10 mg Tablet.
SCOPE:
This SAP gives a detailed outline for the finished product analysis of Vonoprazan 10 mg Tablet and will cover In process testing activities on a physical, chemical & instrumental basis.
RESPONSIBILITY:
QC Analyst is responsible for physical / chemical testing and preparing standard analytical procedure.
It is the responsibility of QC Manager to assist and ensure Testing Procedure as per SAP and to make certain that this SAP is followed in its entirety, reviewed regularly and revised as necessary.
REFERENCE:
INNOVATORS SPECIFICATIONS
MATERIAL AND EQIUPMENT:
- UV Spectrophotometer
- HPLC
- Dissolution apparatus
- Friability apparatus
- Hardness apparatus
- Disintegration Tester
- Vernier Caliper
- Analytical Balance
- Moisture analyzer
- Mortar and pestle
- Spatula
- Filter Paper
- Magnetic Stirrer & Hot Plate
- Sonicator
- Vacuum Pump
- Glassware
- Potassium dihydrogen phosphate
- Ammonium acetate
- Methanol
Identification: Confirm the identity of the active ingredient and other excipients used in the formulation. Use validated analytical methods such as high-performance liquid chromatography (HPLC) or gas chromatography (GC) to determine the purity and identity of the ingredients.
Assay: Determine the amount of Vonoprazan Fumarate in the tablet using a validated analytical method such as HPLC and UV. The assay should be performed to ensure that the amount of the active ingredient is within the acceptable range.
Dissolution: Test the dissolution rate of the Vonoprazan Fumarate tablet using USP apparatus I or II. The dissolution test measures the rate at which the active ingredient is released from the tablet and becomes available for absorption. The results of the dissolution test are used to ensure that the tablet is formulated to release the drug within the required time frame.
Disintegration: Test the disintegration time of the Vonoprazan Fumarate tablet using USP apparatus II. Disintegration testing determines the time required for the tablet to disintegrate into small particles and become available for dissolution. The results of the disintegration test are used to ensure that the tablet disintegrates within the required time frame.
Uniformity of dosage: Perform content uniformity testing to ensure that the amount of Vonoprazan Fumarate in each tablet is consistent. The test should be performed on a representative sample of tablets to ensure that the tablets are uniform in dosage.
Physical tests: Conduct physical tests such as weight variation, hardness, friability, and thickness to ensure that the Vonoprazan Fumarate tablets meet the required specifications. These tests determine the tablet’s physical properties, including its weight, size, and strength.
Stability: Conduct stability studies to determine the shelf life and storage conditions of the Vonoprazan Fumarate tablets. The stability studies should be performed under various environmental conditions to simulate the expected storage conditions.
PROCEDURE:
FINAL MIX
Description:
white powder.
Procedure: Take 2.0 g of the test sample in a watch glass and observe visually with black background. Check the appearance of color, nature and any visible foreign particles.
Identification:
The retention time of the major peak of the sample solution correspond to that of the standard solution as obtained in the assay
Loss on Drying: (By Moisture Analyzer)
Procedure:
Turn on instrument 20 minute before the test. Take 2 g powder spread uniformly on Moisture Analyzer plate. Close the lid and press start button.
NMT 3.0% when determined by LOD Apparatus, Use 2.0 g of powder.
Assay: (Limit: 90%-110%) Compression Weight of Powder/Tablet: 150 mg /tablet
Procedure:
Buffer Solution: Take 2.5g of ammonium acetate to1000 mL of water. Adjust pH to 4.0 ± 0.2 units.
Mobile Phase: Methanol and Buffer Solution (50:50)
Diluent: Mobile Phase
Standard Stock Solution:
Take 26.7 mg of Vonoprazan Fumarate WS equivalent to 20mg of Vonoprazan and add about 2% of Dimethylsulphoxide of the total volume, makeup the volume up to 50 mL in volumetric flask with diluent and sonicate for 3 minutes to facilitate dissolution.
Standard Solution:
Transfer the 5mL of stock solution to 50mL volumetric flask and make up volume with Diluent. Pass through a suitable filter.
Sample solution:
Take compression weight of finally grinded granules equivalent to 20 mg of Vonoprazan in 50 mL volumetric flask, add about 2% of Dimethyl sulphoxide to the total volume and dissolved in diluent. Shake by mechanical mean for 10 minutes to disperse and allow any insoluble matter to settle.
Transfer the 5mL of stock solution to 50mL volumetric flask and make up volume with diluent.
Pass through a membrane filter of 0.45-µm pore size.
Chromatographic Conditions:
SOP for Vonoprazan 10 mg Tablet Testing Procedure
Detector: UV 254 nm
Column: 4.6-mm x 15-cm; packing L1
Column Temperature: 30±1°C
Flow Rate: 1 mL/min
Injection Volume: 20 µL
System Suitability:
Samples: Standard solution
Tailing Factor: NMT 2.0 for the Vonoprazan peak, standard solution.
Theoretical Plates: Not less than 2000
Relative standard deviation: NMT 2.0 % standard solution.
Calculations:
Sample Area Under Curve x Standard Concentration x Ave. Weight of Tablet x Potency
Standard Area Under Curve x Sample Concentration x Label Claim
Limit: Vonoprazan as Fumarate: 90%-110%of the labeled amount
Hardness Test & Dimensions:
Perform the hardness test on 10 tablets and take the average. Power on the instrument and regulate zero adjustment and preset the ‘’HARDNESS’’ and “Thickness” mode. Place the tablet on the test plate, begin testing and read the hardness thickness and diameter. Clean the shattered tablet and print out test results, perform the test on 10 tablets and take the average.
Hardness Standard Limit: 5kg – 10kg
Friability Test:
For tablets with a unit mass equal to or less than 650 mg, take a sample of whole tablets corresponding to 6.5 g. For tablets with a unit mass of more than 650 mg, 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. Generally, the test is run once. If obviously cracked, cleaved, or broken tablets are present in the tablet sample after tumbling, the sample fails the test. If the results are doubtful or if the weight loss is greater than the targeted value, the test should be repeated twice and the mean of the three tests determined. A maximum mean weight loss from the three samples of not more than 1.0% is considered acceptable for most products.
% FRIABILITY= W1-W2/W1 x 100
Disintegration Test:
Place the beaker filled with water into the beaker stand inside the bath and. Switch on the instrument, set the temperature at 37ºC± 2º C and wait till the temperature of the beaker reaches to the 37ºC± 2º C. Engage the basket on basket hook put the tablets in 6 tubes individually and place the discs then start the oscillations and timer. Note the disintegration time of all the six tablets.
Note the Disintegration time of 1st tablet to the last tablet.
Disintegration Time: NMT 15 minutes at 370C ± 20C
Acceptance criteria of disintegration for tablets:
If 1 or 2 tablets fail to disintegrate completely repeat the test on 12 additional tablets, not less than 16 of the totals of 18 tablets tested disintegrate completely.
Dissolution Test:
Buffer Solution pH 6.8: Dissolve 6.8045 g of KH2PO4 dissolved in 500 mL of water. Add 112 mL 0.2 Molar sodium hydroxide and volume make up to 1000 mL with water. Adjust with phosphoric acid to a pH of 6.8, if necessary.
USP Apparatus: USP Apparatus II Peddle
Medium: 900mL Buffer pH 6.80
Speed: 50 rpm
Time: 30 Minutes
Medium Temperature: 37ºC ± 0.5ºC
Diluent: Buffer Medium
Standard stock solution: Take 29.6 mg of Vonoprazan Fumarate WS equivalent to 22.2mg of Vonoprazan in 100 mL volumetric flask and dissolved in diluent Shake, and sonicate for 3 minutes to facilitate dissolution.
Standard solution: Transfer the 1mL of stock solution to 20mL volumetric flask in Buffer pH 6.80. Pass through a suitable filter.
Sample solution: Take 20 mL of sample pass through a suitable filter and use.
Instrumental Conditions
Mode: UV
Analytical wavelength: UV 254 nm
Cell length: 1cm
Blank: Medium
System suitability
Samples: Standard solution
Calculations
Calculate the amount of Vonoprazan dissolved by the formulae;
Result = (Au/As) x Cs x V x (1/L) X 100
Where,
Au= Absorbance of sample
As = Absorbance of WS
Cs= concentration in mg/ml of the working standard solution.
V = volume in ml of medium (900mL)
L = label claim (mg/Tablet).
Tolerance
The amount of drug dissolve in solution for each tablet is not less Than 80% (Q) of the amount stated on the label for Vonoprazan at 30 minutes.
Acceptance criteria
| Stage | Number Tested | Acceptance criteria |
| S1 | 6 | Each unit is not less than Q + 5%. |
| S2 | 6 | Average of 12 units (S1 + S2) is equal to or greater than Q, and no unit less than Q – 15%. |
| S3 | 12 | Average of 24 units (S1 + S2 + S3) is equal to or greater than Q, not more than 2 units are less than Q– 15%, and no unit is less than Q – 30%. |
Leak Test
Take 06 blisters of tablet 03 filled and 03 empty. Dip these blisters in the bowl of leak test apparatus containing colored water. Create vacuum 250 mmHg and hold for one minute. Release vacuum and check the penetration of water inside the blisters. All blisters should be free of water.