Testing the finished product of Clopidogrel 75 mg + Aspirin 75 mg tablets involves various quality control measures to ensure the safety, efficacy, and consistency of the medication.
CLOPIDOGREL 75 mg + ASPIRIN 75 mg Tablet Finish Product Testing Procedure is important to note that this is a general overview of the testing procedure, and specific requirements may vary based on the country, regulatory guidelines, and the particular version of the monograph being followed. Always consult the relevant monographs, guidelines, and validated testing procedures for accurate and reliable testing of Clopidogrel 75 mg + Aspirin 75 mg tablets.
Here is a general outline of the testing procedure for Clopidogrel 75 mg + Aspirin 75 mg tablets:
PURPOSE:
To describe the procedure for analysis at the in-process and finished stage of CLOPIDOGREL 75 mg + ASPIRIN 75 mg Tablet Finish Product Testing Procedure.
SCOPE:
This SAP gives a detailed outline for the finished product analysis of CLOPIDOGREL 75 mg + ASPIRIN 75 mg Tablet Finish Product testing Procedure 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:
- HPLC
- Dissolution apparatus
- Friability apparatus
- Hardness apparatus
- Disintegration Tester
- Vernier Caliper
- Analytical Balance
- pH meter
- Moisture analyzer
- Mortar and pestle
- Spatula
- Filter Paper
- Magnetic Stirrer & Hot Plate
- Sonicator
- Vacuum Pump
- Glassware
- Methanol HPLC Grade
- Hydrochloric acid
- Distilled water
PROCEDURE:
FINAL MIX
CLOPIDOGREL 75 mg + ASPIRIN 75 mg Tablet Finish Product Testing Procedure
Description:
A 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: (By HPLC)
The retention time of major peak of the sample preparation corresponds to that of the standard preparation 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 5.0% when determined by LOD Apparatus, Use 2.0 g of powder.
Assay: (Limit: 90%-110%).
Assay Procedure:
Mobile Phase:
Methanol and Distilled Water (800:200)
Diluent: Mobile phase
Standard Stock solution: Take 75 mg aspirin WS and 97.8mg of clopidogrel hydrogen sulfate WS equivalent to 75 mg of clopidogrel into a 100 volumetric flask. Add diluent, and shake for up to 2 minute to disperse. Following dispersion, sonicate for 3 min, and shake for 2 min. Dilute with diluent to volume.
Standard solution: Take 2 mL from the standard stock solution in 100mL volumetric flask and make up volume with diluents. Pass through a membrane filter of 0.45-µm pore size.
Sample stock solution: Weigh and finely powder 10 g of granules. Transfer a portion of the powder, equivalent to75 mg of aspirin and 75 mg of clopidogrel into a 100 volumetric flask. Add diluent, and shake for up to 2minute to disperse. Following dispersion, sonicate for 3 min, and shakefor2 min. Dilute with diluents to volume. Filter the solution.
Sample solution: Take 2 mL from the filtrate in 100mL volumetric flask and make up volume with diluents. Pass through a membrane filter of 0.45-µm pore size.
Chromatographic system
Mode: LC
Detector: UV 225 nm.
Column: 4.6-mm x 25-cm; 5-µm packing L1
Temperatures: Column: 30°C
Flow rate: 1.0 mL/min
Injection volume:20 µL
System Suitability:
Samples: Standard solution
Tailing Factor: NMT2.0 for Aspirin and Clopidogrel
Relative standard deviation: NMT 2.0% for Aspirin and Clopidogrel
Calculations:
Average Sample AUC x Standard Concentration x Ave. Weight of Tablet x Potency
Average Standard AUC x Sample Concentration x Label Claim x Factor
(Limit: Aspirin and Clopidogrel: 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: 7 Kg – 20 Kg
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 x 100/W1
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 tablet fail to disintegrate completely repeat the test on 12 additional tablets, not less than 16 of the total of 18 tablets tested disintegrate completely.
Dissolution Test:
Normal Hydrochloric Acid: Dissolve 8.5 mL of Hydrochloric acid to 1000mL beaker and volume make up up to 1000 mL with Water.
Hydrochloric Acid Buffer pH 3.0:
14.91g/L of potassium chloride ± 45mL 0.1N HCl make up volume 1000mL with water.
USP Apparatus: USP Apparatus II Peddle
Medium: 900mL (0.1N HCl)
Speed: 75 rpm
Time: 45 Minutes
Medium Temperature: 37º ± 0.5º
Recommended Sampling Time: Aspirin and clopidogrel: 45 Minutes
Diluent: Dissolution medium
Standard solution:
Take 40 mg aspirin WS and 52.1 mg of clopidogrel hydrogen sulfate WS equivalent to 40 mg of clopidogrel into a 50 volumetric flask, then make up volume with medium.
Take 5 mL from standard stock solution and make up the volume upto50 mL with medium. Pass through a membrane filter of 0.45-µm pore size.
Sample solution: Pass a portion of solution under through a suitable filter of 0.45-um pore size.
Mobile Phase:
Methanol and Distilled Water (750:250)
Chromatographic system
Mode: LC
Detector: UV 225 nm.
Column: 4.6-mm x 25-cm; 5-µm packing L1
Temperatures: Column: 30°C
Flow rate: 1.0 mL/min
Injection volume: 20 µL
Calculations:
Sample AUC x Standard Concentration x Potency
Standard AUC x Sample Concentration
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 aspirin and clopidogrelat20 minute.
Assay Test By HPLC:
Procedure:
Mobile Phase:
Methanol and Distilled Water (800:200)
Diluent: Mobile phase
Standard Stock solution: Take 75 mg aspirin WS and 97.8mg of clopidogrel hydrogen sulfate WS equivalent to 75 mg of clopidogrel into a 100 volumetric flask. Add diluent, and shake for up to 2 minute to disperse. Following dispersion, sonicate for 3 min, and shake for 2 min. Dilute with diluent to volume.
Standard solution: Take 2 mL from the standard stock solution in 100mL volumetric flask and make up volume with diluents. Pass through a membrane filter of 0.45-µm pore size.
Sample stock solution: Grind not less than 10 tablets to fine powder. Transfer a portion of the powder, equivalent to75 mg of aspirinand 75 mg of clopidogrel into a 100 volumetric flask. Add diluent, and shake for up to 2 minute to disperse. Following dispersion, sonicate for 3 min, and shake for 2 min. Dilute with diluent to volume. Filter the solution.
Sample solution: Take 2 mL from the filtrate in 100mL volumetric flask and make up volume with diluents. Pass through a membrane filter of 0.45-µm pore size.
Chromatographic system
Mode: LC
Detector: UV 225 nm.
Column: 4.6-mm x 25-cm; 5-µm packing L1
Temperatures: Column: 30°C
Flow rate: 1.0 mL/min
Injection volume: 20 µL
System Suitability:
Samples: Standard solution
Tailing Factor: NMT 2.0 for Aspirin and Clopidogrel
Relative standard deviation: NMT 2.0% for Aspirin and Clopidogrel
Calculations:
Average Sample AUC x Standard Concentration x Ave. Weight of Tablet x Potency
Average Standard AUC x Sample Concentration x Label Claim x Factor
(Limit Aspirin and Clopidogrel: 90%-110%of the labeled amount)
BLISTER STAGE:
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.
CONTENT UNIFORMITY TEST: By Weight variation
Calculations of Assay:
Average Sample AUC x Standard Concentration x Ave. Weight of Tablet x Potency
Average Standard AUC x Sample Concentration x Label Claim x Factor
Calculation of Acceptance Value (AV):
Limits:
L1= ≤ 15 (For 10 Unit)
L2= ≤ 25 (For 30 Unit)
General Formula = M-x̄ ±ks
Acceptability Constant = (k)
Standard Deviation (SD) = s
Number of Units = (n)
Reference Value = M
Mean of Individual Content = x̄