To determine Sumatriptan succinate (85mg) and Naproxen sodium (500mg) in a tablet formulation, both UV spectrophotometry and HPLC methods can be utilized. Sumatriptan as Succinate 85mg and Naproxen Sodium 500mg Tablet Testing Procedure By UV and HPLC Method Here’s an outline of the testing procedures for each method:
PURPOSE
To describe the procedure for analysis at the in-process and finished stage of Sumatriptan as Succinate 85mg per Tablet and Naproxen Sodium 500mg per Tablet Tablet.
SCOPE
This SAP gives a detailed outline for the finished product analysis of Sumatriptan as Succinate 85mg per Tablet and Naproxen Sodium 500mg per 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
INNOVATOR’S 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
- Ortho- Phosphoric Acid
- Acetonitrile
- Potassium Dihydrogen Phosphate
PROCEDURE
Final Mix
Sumatriptan as Succinate 85mg and Naproxen Sodium 500mg Tablet Testing Procedure By UV and HPLC Method
Description
A white to off white granular 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 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 Analyzerplate. 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%)
Procedure:
Buffer Solution: Dissolve 1 mL ortho phosphoric acid to1000 mL of water. Mix and sonicate.
Mobile Phase: Acetonitrile and Buffer Solution (50:50)
Diluent: Mobile phase
Standard Solution
Take 29.7 mg of Sumatriptan Succinate WS equivalent to 21.2 mg of Sumatriptan and 125 mg ofNaproxen Sodium WS,dissolved in 100 mL volumetric flask, dilute with diluent to volume. Shake and Pass through a suitable filter.
Transfer the 2 mL of stock solution to 50mL volumetric flask and make up volume with diluent.
Sample solution
Take weight of finally grinded granules equivalent to 42.5 mg of Sumatriptan and 500mg of Naproxen Sodium in 100 mL volumetric flask and dissolved in diluent. Shake by mechanical mean for 5 minutes to disperse and allow any insoluble matter to settle.
Transfer the 2mL 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
Detector: UV 283 nm
Column: 4.6-mm x 15-cm; packing L1
Column Temperature: 30±1°C
Flow Rate: 1.0 mL/minute
Injection Volume: 20 µL
System Suitability
Samples: Standard solution
Tailing Factor: NMT 2.0
Theoretical Plates: Not less than 1500
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: Sumatriptan and Naproxen Sodium: 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: Not more than 15.00 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 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 I Basket
Medium: 900mL Buffer pH 6.80
Speed: 75 rpm
Time: 45 Minutes
Medium Temperature: 37ºC ± 0.5ºC
Injection Volume: 20 µL
Diluent: Acetonitrile and Distilled Water (50:50)
Mobile phase and System suitability: Proceed as directed in the assay.
Chromatographic Conditions:
As directed in assay
Take 33 mg of Sumatriptan Succinate WS equivalent to 23.6 mg of Sumatriptan and 138.9 mg of Naproxen Sodium WS, dissolved in 50 mL volumetric flask, dilute with diluent to volume. Shake and Pass through a suitable filter.
Transfer the 2 mL of stock solution to 50mL volumetric flask and make up volume with Buffer pH 6.80.
Sample solution: Take 20 mL of sample pass through a suitable filter.
Transfer the 5mL of stock solution to 25mL volumetric flask and make up volume with Buffer pH 6.80.
Tolerance: The amount of drug dissolve in solution for each tablet is not less than 75% (Q) of the amount stated on the label for Sumatriptan Succinatea nd Naproxen Sodium at 45 minutes.
Acceptance criteria
| Stage | Number Tested | Acceptance criteria |
| S1 | 6 | Each unit is not less than Q + 5%. |
| S1 | 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%. |
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.
Finished Product Test
Definition
Tablet contain NLT 90.0% and NMT 110.0% of the labeled amount of Sumatriptan and Naproxen Sodium.
Label Claim
Sumatriptan as Succinate…………. 85 mgper Tablet
Naproxen Sodium……………. 500 mgper Tablet
Uniformity of Dosage Units
Proceed as directed in Compression stage
Standard Limit: ± 5.00%
Hardness Test & Dimensions
Proceed as directed in Compression stage
Hardness Standard Limit: Not more than 15.00 Kg
Content Uniformity Test
Buffer Solution: Same as for assay
Calculation of Acceptance Value (AV)
Limits:
L1= ≤ 15 (For 10 Unit)
L2= ≤ 25 (For 30 Unit)
General Formula = M-x̄ + ks