MFR of Aceclofenac 100 mg and Paracetamol 325 mg Tablets
TABLE OF CONTENTS
| S.NO. | TITLE | Page No | |
| 1.0 | PRODUCT DETAILS | ||
| 2.0 | MANUFACTURING FORMULA | ||
| 3.0 | LIST OF EQUIPMENTS | ||
| 4.0 | MANUFACTURING INSTRUCTIONS | ||
| 5.0 | GENERAL PRECAUTIONS | ||
|
6.0 | MANUFACTURING PROCESS DETAILS | ||
| 6.1 | GRANULATION | ||
| 6.2 | COMPRESSION | ||
| 6.3 | COATING | ||
1.0 PRODUCT DETAILS:
| Product Name | Aceclofenac and Paracetamol Tablets |
| Product Description | Orange color, elongated biconvex, film coated tablet having one side mid break line and other side plain |
| Strength | Aceclofenac 100 mg and Paracetamol 325 mg |
| Label claim
| Each film coated tablet contains: Aceclofenac IP – 100 mg Paracetamol IP – 325 mg |
| Batch Size | 3,00,000 Tablets |
| Average Weight | 580 mg |
| Shelf Life | 24 months |
| Storage | Store in a cool, dry and dark place below 250C |
| Drug Category | Anti-Inflammatory Drug |
2.0 MANUFACTURING FORMULA:
| Material Name | Grade | Category | Quantity per Unit (In mg) | Overages | Batch Qty. (In kg) |
| Dry Mixing | |||||
| Aceclofenac | IP | API | 100 mg | —- | 30.000 kg |
| Paracetamol | IP | API | 325 mg | —- | 97.500 kg
|
| Starch | IP | Diluent | 50.00 mg | —- | 15.000 kg |
| MCCP Plain | IP | Diluent | 61.59 mg | —- | 18.477 kg |
| Binder | |||||
| PVPK-30 | IP | Binder | 3 mg | —- | 0.900 kg |
| Sodium Benzoate | IP | Preservative | 1.16 mg | —- | 0.348 kg |
| Gelatin | IP | Binder | 3 mg | —- | 0.900 kg |
| Starch | IP | Binder | 16.25 mg | —- | 4.875 kg |
| Purified Water | IP | Solvent | 0.160 ml | —- | 48.000 liter |
| Lubricant | |||||
| Talcum | IP | Anti-caking agent | 10 mg | —- | 3.000 kg |
| Sodium Starch Glycolate | IP | Disintegrants | 8 mg | —- | 2.400 kg |
| Magnesium Stearate | IP | Anti- Adherent | 2 mg | —- | 0.600 kg |
3.0 LIST OF EQUIPMENTS:
| Sr. No. | Machineries/equipments | Capacity | Equipment ID. |
| 1. | Weighing Balance | 300 kg ,100 kg | |
| 2. | Sifter (with SS Sieves No’s 16,20,30,60 and 100) | 30” | |
| 3. | Paste Kettle with stirrer | 60 liter | |
| 4. | Stirrer for binder preparation | — | |
| 5. | Multi-Mill (screen size 8 mm, 2 mm) | — | |
| 6. | Rapid Mixer Granulator (RMG ) | 160 liter | |
| 7. | Fluid Bed Dryer (FBD) | 120 kg | |
| 8. | Octagonal Blender | 500 liter | |
| 9. | Compression Machine | 27 Station | |
| 10. | SS Containers with lid | 10 liter,30 liter and 100 liter | — |
| 11. | Halogen Moisture Balance | — | |
| 12. | Poly-lined HDPE Containers with lid | 30 liter and 45 liter | — |
4.0 MANUFACTURING INSTRUCTIONS:
- Aceclofenac API Description: A white or almost white crystalline powder.
- Paracetamol API Description: A white crystals or a white crystalline powder.
- All the manufacturing activities shall be performed under controlled conditions (temperature NMT 25 0C and relative humidity NMT 60%).
- When working with Active Ingredients and drug product or mixture of Active Ingredients and Excipients, wear gloves and mask to avoid exposure and contact with any body parts.
5.0 GENERAL PRECAUTIONS:
- All the Activity shall be performed as per current SOPs.
- Follow the GMP compliance throughout the manufacturing process
- Take the line clearance from QA before starting the manufacturing operation during batch to batch and product to product change over.
- Do not overwrite the entry, in case there is correction, cancel the entry by single line with sign & date and make correct entry
MANUFACTURING PROCESS DETAILS:
6.1 GRANULATION:
STEP – I (SIFTING):
- Check Sieve Integrity (before sifting and after sifting).
- Set the Sifter and sieve the Dispensed Materials as per Sieve Sizes mentioned below:
| Material Name | Std. Qty. (kg) | Sieve No. |
| Dry Mixing | ||
| Aceclofenac IP | 30.000 kg | 16 # |
| Paracetamol IP | 97.500 kg | 16 # |
| Starch IP | 15.000 kg | 100 # |
| MCCP Plain IP | 18.477 kg | 60 # |
| Binder | ||
| PVPK-30 IP | 0.900 kg | —- |
| Sodium Benzoate IP | 0.348 kg | —- |
| Gelatin IP | 0.900 kg | —- |
| Starch IP | 4.875 kg | 100 # |
| Lubricant | ||
| Talcum IP | 3.000 kg | 60 # |
| Sodium Starch Glycolate IP | 2.400 kg | 60 # |
| Magnesium Stearate IP | 0.600 kg | 30 # |
- Collect the sifted Aceclofenac IP (30.000 kg), Paracetamol IP (97.500 kg), Starch IP (15.000 kg) and MCCP Plain IP (18.477 kg) into four Poly-lined HDPE Container (capacity: 45 liter each) two equal parts for LOT I and LOT II.
- Collect the sifted Starch IP (4.875 kg) in SS Container (capacity: 10 liter)
- Collect the sifted Talcum IP (3.000 kg) and Sodium Starch Glycolate IP (2.400 kg) in Poly-lined SS Container (capacity : 10 liter)
- Collect the sifted Magnesium Stearate IP (0.600 kg) in Poly-lined SS Container (capacity: 10 liter)
- Divide the sifted material Aceclofenac IP (30.000 kg), Paracetamol IP (97.500 kg), Starch IP (15.000 kg) and MCCP Plain IP (18.477 kg) in two equal parts for LOT-I and LOT-II.
STEP – II (DRY MIXING): FOR LOT – I:
Transfer the sifted Aceclofenac IP (15.000 kg ), Paracetamol IP (48.750 kg ), Starch IP (7.500 kg) and MCCP Plain ( 9.238 kg ) in RMG ( capacity : 160 liter) and dry mix the materials till uniform mixing.
Mixing Time = 8 minutes.
Mixing Speed: 03 minutes at slow speed and 05 minutes at fast speed.
STEP – III – (BINDER PREPARATION): FOR LOT –I & LOT- II:
(a) Take purified water (42.00 liter) in Paste Kettle, heat the purified water at 800C and add Gelatin IP (0.900 kg).
(b) Take purified water (5.00 liter, at temperature 250C) in SS Container (capacity: 30 liter) and add Starch IP (4.875 kg) slowly with continuously stirring till uniform solution is ready.
(c) Add the above solution of Step – III (b) in solution of Step – III (a) in Paste Kettle with continuously stirring till uniform paste is ready.
(d) Take purified water (1.000 liter, at temperature 35°C) separately in SS Container (capacity: 10 liter) and add Sodium Benzoate IP (0.348 kg) and PVPK-30 IP (0.900 kg) and mix one by one with stirrer till dissolved properly in water and then add to Step – III (c) and continuously stirring till final paste is ready and cool the paste to 35°C to 40°C.
(e) Divide paste into two equal parts for LOT – I and LOT – II in SS Containers (capacity: 30 liter each).
STEP –IV (BINDING OF DRY MIX MATERIAL) : FOR LOT – I:
Slowly add the binder of Step-III in dry mix materials of Step – II in Rapid Mixer Granulator (capacity: 160 liter) with running at slow speed impeller (13 ampere) for 5 minutes. Then run impeller and chopper both at medium speed (15 ampere) for 10 min and finally run both chopper and impeller on fast speed (19 ampere) for 3 minutes till uniform mixing. Unload the material in SS Container (capacity: 100 liter) from RMG.
Mixing Time: 18 minutes
Ampere Load of Impeller: 13 to 19 ampere.
STEP-V (WET SCREENING) : FOR LOT – I:
Take wet material from SS Container (capacity: 100 liter) and pass through Multi-Mill with 8 mm screen and collect the wet material in a FBD bowl.
STEP –VI – (DRYING) : FOR LOT- I:
Dry the wet material of Step-V in FBD (capacity: 120 kg) till the LOD of granules is achieved between 2.5 to 3.0 % at 105°C checking by Halogen Moisture Balance.
Inlet Temperature: 55°C.
Outlet Temperature : To be established
Bed Temperature: To be established
Raking Frequency: After 30 minutes
Drying Time: 2 hours.
STEP-VII- (SIZING/MILLING) : FOR LOT – I:
Check Screen Integrity (before sifting and after sifting).
Milled the dried material of Step -VI through Multi Mill using screen size 2 mm and collect milled material in one SS Containers (capacity :100 liter ). After milling transfer the milled material into four Poly-lined HDPE Containers (capacity: 30 liter each) and weight and record the milled granules weight.
Blade Type: Both (Knife blades/Scraping blades)
Rotor Speed: 2000 RPM
NOTE:
FOR LOT – II: Please follow the same procedure of LOT – I of dry mixing, binding of dry mix material, wet screening, drying and sizing/ milling.
STEP – VIII (PRE –LUBRICATION):
Load the milled granules of Step-VII of LOT- I and LOT – II in Octagonal Blender (capacity: 500 liter) and add sifted Talcum IP (3.000 kg) and Sodium Starch Glycolate IP (2.400 kg), mix properly till uniform mixing of Pre-Lubricating Material.
Mixing Time: 30 minutes (15 minutes clockwise direction and 15 minutes anti-clockwise direction)
Mixing Speed: 10 RPM
STEP – IX (LUBRICATION):
Add the sifted Magnesium Stearate IP (0.600 kg) in Step-VIII of Pre- Lubricated Material and mix properly till uniform mixing of materials with Magnesium Stearate IP.
Mixing Time: 05 minutes. (clockwise direction)
Mixing Speed: 10 RPM.
STEP- X (BLEND SAMPLE ANALYSIS):
After completion of lubrication, collect the composite blend sample and send to QC for analysis according to the table below:
| Test | Specification |
| Appearance of blend Blend Uniformity Blend Assay LOD Bulk Density Tapped Density Compressibility Index Hausner Ratio | White color free flowing granular powder 90 % to 110 % 98 % to 103 % 2.0 % to 3.0 % 0.7692 gm/ml 0.9677 gm/ml 20.3788 % (Fair) 1:2581 (Fair) |
STEP – XI:
Unload the above blended material and weight and store in seven Poly-lined HDPE Containers (capacity: 30 liter each).
STEP – XII:
Clean all equipments used in the granulation as per respective equipment cleaning SOP.
- COMPRESSION:
STEP – I:
After receiving QC approval for blend, compress the blend as per the following parameters and In-Process checks under controlled environmental condition.
| S. No. | Parameters | Standard | No. of Tablets | In-Process Frequency |
| 1. | Feed frame alignment and adjustment | Should be satisfactory | —– | —– |
| 2. | Lower Weight Assembly | Should be satisfactory | —– | —– |
| 3. | Hydraulic Pressure
| 6 -8 Tones (D-Tooling, 27station Compression Machine) | —– | —– |
| 4. | Machine Speed | 15 RPM to 18 RPM | —– | —– |
| 5. | Upper Punch Size | 15 mm with break line | —– | —– |
| 6. | Lower Punch Size | 7.5 mm | —– | —– |
| 7. | Length of Tablets. | 15 mm | —– | —– |
| 8. | Width of Tablets | 7.5 mm | 6/Individual | 2 hours |
| 9. | Thickness of Tablets | 6.61 mm ±.2 mm | 6/Individual | 2 hours |
| 10. | Weight of 20 Tablets | 11.600 gm. ± 3% | 20/Composite | 30 minutes |
| 11. | Product Description | White color, elongated biconvex, uncoated tablet having one side mid break line and other side plain | 20/Composite | 2 hours |
| 12. | Uniformity of Weight | NMT 02 tablets out of 20 deviate from the average weight by more than 3 % and no single tablet deviates from the average weight by more than 5 % | —– | 01 hour |
| 13. | Average Weight of Tablets | 580 mg ± 2 % | 20/Individual | 30 minutes |
| 14. | Hardness | NLT 4 kg/cm2 | 6/Individual | 30 minutes |
| 15. | Disintegration Time | NMT 15 min | 6/Composite | 01 hour |
| 16. | Friability | NMT 1% | 20/Composite | 01 hour |
STEP – II:
Send the sample of compressed tablets to QC department for analysis.
STEP – III:
Weight the compressed tablets and store into seven Poly-lined HDPE Containers with lid (capacity: 30 liter each) with proper status label till next step tablet packing.
STEP – IV:
Clean the Compression Machine as per cleaning SOP.
COATING:
STEP – I (COATING MATERIALS DETAILS):
| Sr. No. | Material Name | Batch Quantity (In kg) |
| 1. | Sheffcoat PVA Orange 5Y02059 | 4.350 kg |
| 2. | Purified water IP | 17.400 liter |
STEP-II (LIST OF EQUIPMENTS FOR COATING):
| Sr. No. | Machineries/Equipments | Capacity | Equipment ID. |
| 1. | Coating Pan | 42″ | |
| 2. | Spray Gun | 1.5 mm | — |
| 3. | Filter Cloth 100 # | 0.5 mm | — |
| 4. | Stirrer | — | — |
| 5. | SS Container | 30 liter (03 no’s) | — |
| 6. | Poly-lined HDPE Containers with lid | 30 liter (07 no’s) | — |
STEP – III (PREPARATION OF COATING SOLUTION) FOR LOT -I & LOT- II:
- Take Purified Water IP (17.400 liter) and mix Sheffcoat PVA Orange 5Y02059 (4.350 kg) in SS Container (capacity: 30 liter) and mix properly with stirrer till uniform mixing achieved.
Speed of stirrer: Constant.
- Filter the coating solution with Nylon Filter Cloth 100# (0.5 mm).
- Keep the solution for 30 minutes and after 30 minutes proceed for coating process.
- Divide the coating solution equally into two parts for LOT – I and LOT – II in SS Container (capacity: 30 liter each)
STEP – IV (COATING PROCEDURE OF TABLETS): FOR LOT- I:
- Coating will be done in two lots, divide total compressed tablets into two equal quantities for LOT -I and LOT -II (87.000 kg tablets for each lot).
- Load the tablets of LOT – I (87.000 kg) in coating pan (capacity: 42″), start the hot air blower, set the supply air temperature at 60°C to 65°C and start the exhaust fan & warm the tablets bed 40°C to 45°C.
- After warm up of tablets, take weight of 100 warm tablets for calculation of weight buildup of tablets after coating.
- Set the coating parameter as given in below table and start the coating process by starting coating spray from gun.
| Parameter | Specification | Status |
| No. of Baffles in coating pan | 06 | —- |
| No. of Guns | 02 | —- |
| Gun to Gun Distance | 08 inch | —- |
| Gun to Tablet Bed Distance | 10 inch | —- |
| BED Temperature | 40 0C to 45 0C | —- |
| Pan RPM | 18 to 22 rpm | —- |
| % Weight Gain | 2.0 % | —- |
STEP – V (COATING IN-PROCESS CHECK PARAMETERS): FOR LOT- I:
| S.No. | Parameters | Standard | No. of Tablets | In-Process Frequency |
| 1 | Product Description | Orange color, elongated biconvex, film coated tablet having one side mid break line and other side plain | 20 No. |
After batch completion |
| 2 | Weight of 20 Tablets after coating | 11.832 gm. ± 2 % | 20 No. | |
| 3 | Average Weight after coating | 591.6 mg ± 2% | 20 No. | |
| 4 | Individual Tablets Weight Variation | ± 3% | 20 No. | |
| 5 | Thickness | 6.63 mm ± 0.2 mm | 6 No. | |
| 6 | Disintegration | NMT 30 min. | 6 No. |
NOTE:
FOR LOT – II (COATING PROCEDURE): Please follow the same procedure of LOT – I of coating from Step-IV and Step -V.
STEP – VI:
Send the composite sample of coated tablets of LOT- I and LOT – II to QC department for analysis.
STEP – VII:
Weigh the coated tablets and store the coated tablets into seven Poly-lined HDPE Containers with lid (capacity: 30 liter each) with proper status label till next step tablet packing.
