Diclofenac Sodium SR 100mg Tablet Standard Analytical Procedure
Reference: United States Pharmacopoeia
APPROVAL BLOCK
| Title | Designation | Signature/Date |
| Written By: | Quality Control Analyst | |
| Reviewed By: | Quality Control Manager | |
| Verified By: | Quality Assurance Incharge | |
| Approved By: | Technical Operation Director |
Distribution List
| Sr. # | Department | New revision # | Retrieval Revision # | Signature & Date |
DOCUMENT REVISION CONTROL
| Rev. # | Date | Initiated By | Page # | Nature of Amendment | Done By |
1.0 PURPOSE
2.0 SCOPE
3.0 RESPONSIBILITY
4.0 REFERENCE
5.0 MATERIAL AND EQIUPMENT
6.0 PROCEDURE
7.0 RISK ANALYSIS
1.0 PURPOSE:
To describes the procedure for analysis at in-process and finished stage of Diclofenac Sodium SR 100mg Tablet.
2.0 SCOPE:
This SAP gives detailed outline for the finished product analysis of Diclofenac Sodium 100mg Tablet and will cover In process testing activities on physical, chemical & instrumental basis.
3.0 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.
4.0 REFERENCE:
USP 44 NF 39
5.0 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 Ammonium Acetate
- Acetonitrile HPLC Grade
- Methanol HPLC Grade
- Distilled water
- Phosphoric acid
- Monobasic Potassium phosphate
- Ammonium Acetate
6.0 PROCEDURE:
6.1 FINAL MIX
6.1.1 Description:
White to off white colored granular powder.
6.1.1.1 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.
6.1.2 Identification: (By HPLC)
A- The retention time of the major peak in the chromatogram of the assay sample preparation corresponds to that in the chromatogram of the standard preparation as obtained in the assay.
B- The UV (190-400 nm) spectrum of the diclofenac peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
6.1.3 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.
6.1.4 Assay: (Limit: 90%-110%)Compression Weight of Powder/Tablet: ___ mg /tablet
6.1.4.1 Procedure:
Solution A: 0.7708 g/L of ammonium acetate in water. Adjust with acetic acid to a pH of 5.3. Pass through a suitable filter of 0.2-um pore size.
Solution B: Acetonitrile
Mobile phase: See Table 1.
Table 1
| Time (Minute） | Solution A (%) | Solution B (%) |
| 0 | 70 | 30 |
| 0.5 | 70 | 30 |
| 8.5 | 5 | 95 |
| 10 | 5 | 95 |
| 10.01 | 70 | 30 |
| 14 | 70 | 30 |
Diluent: Acetonitrile and water (50:50)
Standard solution: 0.2 mg/mL of USP Diclofenac Sodium RS in Diluent
Sample solution: Nominally 0.2 mg/mL of diclofenac sodium in Diluent prepared as follows. Transfer a suitable portion of diclofenac sodium to a suitable volumetric flask from NLT 20 finely powdered Tablets. Add Diluent equivalent to 50% of the flask volume. Dissolve with sonication for 25 min at 45° and fill with Diluent to volume. Pass the solution through a suitable filter of 0.22-um pore size.
[NOTE-Protect the Standards solution and Sample solution from light.]
6.1.4.2 Chromatographic system
- Mode: LC
- Detector: UV 280 nm. For Identification test B, use a photo-diode array detector.
- Column:10-cm x 2.0-mm; 1.9-um packing L1
- Column Temperatures: 35°C
- Flow rate:0.3 mL/min
- Injection volume: 1 µL
6.1.4.3 System Suitability:
Samples: Standard solution
Tailing Factor: NMT 1.2
Relative standard deviation: NMT 2.8%.
6.1.4.4 Calculations:
Average Sample AUC x Standard Concentration x Ave. Weight of Tablet x Potency
Average Standard AUC x Sample Concentration x Label Claim
(Limit for Diclofenac Sodium: 90%-110%of the labeled amount)
6.1.5 ALTERNATE METHOD
6.1.5.1.1 Standard Solution:
Take 50 mg of Diclofenac Sodium WS dissolved in methanol and make up the volume to 50mL with methanol. Shake, and sonicate for 5 minutes to facilitate dissolution.
Take 2 mL from standard stock solution and make up the volume to 100 mL with water.
6.1.5.1.2 Sample solution:
Take weight of finally grinded granules equivalent to 100mg of Diclofenac Sodium and dissolved in methanol and make up the volume to 100mL with methanol. Shake by mechanical mean for 10 minutes to disperse and allow any insoluble matter to settle.
Pass a portion of the sample stock solution through a suitable filter of 0.45um pore size.
Transfer the 2 mL of filtrate to a 100mL volumetric flask make up volume with water. Take reading at UV spectrophotometer at 276 nm using water as blank.
6.1.5.1.3 Calculations:
Sample Absorbance x Standard Concentration x Ave. Weight of Tablet x Potency
Standard Absorbance x Sample Concentration x Label Claim
(Limit for Diclofenac Sodium: 90%-110%of the labeled amount)
6.2 CORE TABLET
6.2.1 Description:
White colored round biconvex shaped bisect tablet.
6.2.2 Compression weight/Tablet:____ mg ±7.5 %
6.2.3 Uniformity of Dosage Units: (By Weight Variation)
Weigh 20 tablets individually and calculate the average weight as: Average weight = (Weight Of 20 Tablets)/20
Weigh all these tablets individually and mark among these weights maximum (WMax) & minimum (WMin) weight tablets. Calculate the maximum and minimum variation in percent as:
Maximum% age variation =((WMax) – (WAvg.))/WAvg×100
Minimum % age variation ((WMin) – (WAvg.))/WAvg×100
Standard Limit: ± 7.5 %
6.2.4 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: NMT 10 Kg
Thickness Standard Limit: ____ mm ± 0.20 mm
Diameter Standard Limit: ____ mm ± 0.20 mm
6.2.5 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
6.3 FILM COATING
6.3.1 Description:
Round biconvex shaped sustain release coated tablet with bisecting line.
Weight/Tablet: ____ mg ± 7.5%
6.3.2 Uniformity of Dosage Units: (By Weight Variation)
Proceed as directed in Compression stage
Standard Limit: ± 7.5%
6.3.3 Hardness Test & Dimensions:
Proceed as directed in Compression stage
Hardness Standard Limit: NMT 10 Kg
Thickness Standard Limit: ___ mm ± 0.20 mm
Diameter Standard Limit: ___ mm ± 0.20 mm
6.3.4 Dissolution Test:
Dissolution Medium:
USP Apparatus: USP Apparatus II Paddle use wire sinkers.
Medium: 0.05 M phosphate buffer, pH 7.5;
Speed: 50rpm
Volume: 900mL
Recommended Sampling Time: Times: 1,5, 10, 16, and 24 h
Diluent: Dissolution medium
Standard solution: Take 27.7 mg of Diclofenac Sodium WS dissolved in medium and make up the volume to 50mL with medium. Shake, and sonicate for 5 minutes to facilitate dissolution
Take 2 mL from standard stock solution and make up the volume to 50 mL with medium.
Analysis: Pass portions of the solution under test through a suitable filter.
Dilute 5mL to 25 mL with Medium.
- Instrumental Conditions
- Mode: UV
- Analytical wavelength: UV 276 nm
- Cell length: 10 mm
- Blank: Medium
- Calculations:
Calculate the amount of Diclofenac Sodium dissolved by the formulae
Result = (Au/As) x Cs x V x D 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),
D = dilution factor of the sample solution
L = label claim (mg/Tablet).
6.3.5 Tolerance:
| Time in hours | Amount Dissolved |
| 1 | 15%-35% |
| 5 | 45%-65% |
| 10 | 65%-85% |
| 16 | 75%-95% |
| 24 | NLT 80% |
The percentages of the labeled amount of diclofenac sodium (C14H10Cl2NNaO2) dissolved at the times specified conform to Acceptance Table 2)
6.3.6 Identification: (By HPLC)
C- The retention time of the major peak in the chromatogram of the assay sample preparation corresponds to that in the chromatogram of the standard preparation as obtained in the assay.
D- The UV (190-400 nm) spectrum of the diclofenac peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
6.3.7 Assay: (Limit: 90%-110%)
6.3.7.1 Procedure:
Solution A: 0.7708 g/L of ammonium acetate in water. Adjust with acetic acid to a pH of 5.3. Pass through a suitable filter of 0.2-um pore size.
Solution B: Acetonitrile
Mobile phase: See Table 1.
Table 1
| Time (Minute） | Solution A (%) | Solution B (%) |
| 0 | 70 | 30 |
| 0.5 | 70 | 30 |
| 8.5 | 5 | 95 |
| 10 | 5 | 95 |
| 10.01 | 70 | 30 |
| 14 | 70 | 30 |
Diluent: Acetonitrile and water (50:50)
Standard solution: 0.2 mg/mL of USP Diclofenac Sodium RS in Diluent
Sample solution: Nominally 0.2 mg/mL of diclofenac sodium in Diluent prepared as follows. Transfer a suitable portion of diclofenac sodium to a suitable volumetric flask from NLT 20 finely powdered Tablets. Add Diluent equivalent to 50% of the flask volume. Dissolve with sonication for 25 min at 45° and fill with Diluent to volume. Pass the solution through a suitable filter of 0.22-um pore size.
[NOTE-Protect the Standards solution and Sample solution from light.]
6.3.7.2 Chromatographic system
Mode: LC
Detector: UV 280 nm. For Identification test B, use a photo-diode array detector.
Column: 10-cm x 2.0-mm; 1.9-um packing L1
Column Temperatures: 35°C
Flow rate: 0.3 mL/min
Injection volume: 1 µL
6.3.7.3 System Suitability:
Samples: Standard solution
Tailing Factor: NMT 1.2
Relative standard deviation: NMT 2.8%.
6.3.7.4 Calculations:
Average Sample AUC x Standard Concentration x Ave. Weight of Tablet x Potency
Average Standard AUC x Sample Concentration x Label Claim
(Limit for Diclofenac Sodium: 90%-110%of the labeled amount)
6.3.8 ALTERNATE METHOD
6.3.8.1.1 Standard Solution:
Take 50 mg of Diclofenac Sodium WS dissolved in methanol and make up the volume to 50mL with methanol. Shake, and sonicate for 5 minutes to facilitate dissolution
Take 2 mL from standard stock solution and make up the volume to 100 mL with water.
6.3.8.1.2 Sample solution:
Take weight of finally grinded granules equivalent to 100mg of Diclofenac Sodium and dissolved in methanol and make up the volume to 100mL with methanol. Shake by mechanical mean for 10 minutes to disperse and allow any insoluble matter to settle.
Pass a portion of the sample stock solution through a suitable filter of 0.45um pore size.
Transfer the 2 mL of filtrate to a 100 mL volumetric flask make up volume with water. Take reading at UV spectrophotometer at 276 nm using water as blank.
6.3.8.1.3 Calculations:
Sample Absorbance x Standard Concentration x Ave. Weight of Tablet x Potency
Standard Absorbance x Sample Concentration x Label Claim
(Limit for Diclofenac Sodium: 90%-110%of the labeled amount)
6.4 BLISTER STAGE:
6.4.1.1 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.
6.5 FINISHED PRODUCT TEST:
6.5.1 Definition:
Diclofenac Sodium 100mg Tablet contains NLT 90.0% and NMT 110.0% of the labeled amount of Diclofenac Sodium.
Label Claim: Diclofenac Sodium100mg per Tablet.
Description:
A film coated round biconvex sustain release tablet with bisecting line pack in unit carton with leaflet.
Weight/Tablet:___ mg ± 7.5 %
6.5.2 Uniformity of Dosage Units: (By Weight Variation)
Proceed as directed in Compression stage
Standard Limit: ± 7.5%
6.5.3 Hardness Test & Dimensions:
Proceed as directed in Compression stage
Hardness Standard Limit: NMT 10 Kg
Thickness Standard Limit: ___ mm ±0.30 mm
Diameter Standard Limit: ___ mm ± 0.20 mm
6.5.4 ASSAY BY HPLC:
6.5.4.1 Proceed as directed in the Film Coating.
6.5.5 DISSOLUTION TEST:
Proceed as directed in the Film Coating.
6.5.6 PACKAGING SPECIFICATIONS:
6.5.6.1 Primary Packaging:
Diclofenac Sodium 100mg Tablet packed in printed Aluminium foil
6.5.7 PACKAGING AND STORAGE:
Store at controlled room temperature, in tight containers, and in a dry place.
7.0 RISK ANALYSIS:
EVIDENCES OF RECORDS & REFERENCES: USP44, NF39
Certificate of Analysis Finished Product
Finished Product QC Number log
Finished Product Batch Analysis Sheet
Finished Product Specification
Product Release Sticker
Raw Data Calculation Sheets