Master Manufacturing Formula (MFR): Aceclofenac 100 mg and Paracetamol 325 mg Tablets
Source: drugsformulations.com via archive.org
TABLE OF CONTENTS
- Product Details
- Manufacturing Formula
- Manufacturing Instructions
- General Precautions
- Manufacturing Process Details
- Granulation
- Compression
- 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 25° C |
| Drug Category | Anti-Inflammatory Drug |
2.0 MANUFACTURING FORMULA
| Section | Material Name | Category | Quantity per Unit (mg) | Overages | Batch Qty. (kg) |
|---|---|---|---|---|---|
| Dry Mixing | Aceclofenac | API | 100 | — | 30.000 |
| Paracetamol | API | 325 | — | 97.500 | |
| Starch | Diluent | 50.00 | — | 15.000 | |
| MCCP Plain | Diluent | 61.59 | — | 18.477 | |
| Binder | PVPK-30 | Binder | — | — | 0.900 |
| Sodium Benzoate | Preservative | 1.16 | — | 0.348 | |
| Gelatin | Binder | — | — | 0.900 | |
| Starch | Binder | 16.25 | — | 4.875 | |
| Binder Solvent | Purified Water | Solvent | 0.160 ml | — | 48.000 liter |
| Lubricant | Talcum | Anti-caking agent | — | — | 3.000 |
| Sodium Starch Glycolate | Disintegrant | — | — | 2.400 | |
| Magnesium Stearate | Anti-Adherent | — | — | 0.600 |
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) | — | |
| 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, 100 liter | |
| 11 | Halogen Moisture Balance | — | |
| 12 | Poly-lined HDPE Containers with lid | 30 liter and 45 liter |
4.0 MANUFACTURING INSTRUCTIONS
- Aceclofenac API: A white or almost white crystalline powder.
- Paracetamol API: A white crystals or a white crystalline powder.
- All the manufacturing activities shall be performed under controlled conditions (temperature NMT 25° C 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.
6.0 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:
| Section | Material Name | Std. Qty. (kg) | Sieve No. |
|---|---|---|---|
| Dry Mixing | Aceclofenac IP | 30.000 | — |
| Paracetamol IP | 97.500 | — | |
| Starch IP | 15.000 | — | |
| MCCP Plain IP | 18.477 | — | |
| Binder | PVPK-30 IP | 0.900 | — |
| Sodium Benzoate IP | 0.348 | — | |
| Gelatin IP | 0.900 | — | |
| Starch IP | 4.875 | — | |
| Lubricant | Talcum IP | 3.000 | — |
| Sodium Starch Glycolate IP | 2.400 | — | |
| Magnesium Stearate IP | 0.600 | — |
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 Containers (capacity: 45 liter each), two equal parts for LOT I and LOT II.
Collect sifted Starch IP (4.875 kg) in SS Container (capacity: 10 liter).
Collect sifted Talcum IP (3.000 kg) and Sodium Starch Glycolate IP (2.400 kg) in Poly-lined SS Container (capacity: 10 liter).
Collect sifted Magnesium Stearate IP (0.600 kg) in Poly-lined SS Container (capacity: 10 liter).
Divide the sifted material Aceclofenac IP, Paracetamol IP, Starch IP and MCCP Plain IP 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.
| Parameter | Specification |
|---|---|
| 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 80° C and add Gelatin IP (0.900 kg).
(b) Take purified water (5.00 liter, at temperature 25° C) 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.
| Parameter | Specification |
|---|---|
| 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.
| Parameter | Specification |
|---|---|
| Inlet Temperature | 55° C |
| Outlet Temperature | To be established |
| Bed Temperature | To be established |
| Raking Frequency | After 30 minutes |
| Drying Time | 2 hours |
| LOD Target | 2.5% to 3.0% at 105°C |
STEP – VII (SIZING/MILLING): FOR LOT – I:
Check Screen Integrity (before sifting and after sifting). Mill the dried material of Step-VI through Multi Mill using screen size 2 mm and collect milled material in one SS Container (capacity: 100 liter). After milling transfer into four Poly-lined HDPE Containers (capacity: 30 liter each) and weigh and record the milled granules weight.
| Parameter | Specification |
|---|---|
| Blade Type | Both (Knife blades/Scraping blades) |
| Rotor Speed | 2000 RPM |
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.
| Parameter | Specification |
|---|---|
| Mixing Time | 30 minutes (15 minutes clockwise + 15 minutes anti-clockwise) |
| Mixing Speed | 10 RPM |
STEP – IX (LUBRICATION):
Add the sifted Magnesium Stearate IP (0.600 kg) and mix properly till uniform mixing.
| Parameter | Specification |
|---|---|
| Mixing Time | 05 minutes (clockwise direction) |
| Mixing Speed | 10 RPM |
STEP – X (BLEND SAMPLE ANALYSIS):
After completion of lubrication, collect composite blend sample and send to QC for analysis:
| Test | Specification |
|---|---|
| Appearance of blend | White color free flowing granular powder |
| Blend Uniformity | 90% to 110% |
| Blend Assay | 98% to 103% |
| LOD | 2.0% to 3.0% |
| Bulk Density | 0.7692 gm/ml |
| Tapped Density | 0.9677 gm/ml |
| Compressibility Index | 20.3788% (Fair) |
| Hausner Ratio | 1.2581 (Fair) |
STEP – XI: Unload the above blended material and weigh and store in seven Poly-lined HDPE Containers (capacity: 30 liter each).
STEP – XII: Clean all equipment used in the granulation as per respective equipment cleaning SOP.
6.2 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.
| Parameter | Standard | No. of Tablets | In-Process Frequency |
|---|---|---|---|
| Feed frame alignment and adjustment | Should be satisfactory | — | — |
| Lower Weight Assembly | Should be satisfactory | — | — |
| Hydraulic Pressure | 6 – 8 Tones (D-Tooling, 27 station Compression Machine) | — | — |
| Machine Speed | 15 RPM to 18 RPM | — | — |
| Upper Punch Size | 15 mm with break line | — | — |
| Lower Punch Size | 7.5 mm | — | — |
| Width of Tablets | 7.5 mm | 6/Individual | 2 hours |
| Thickness of Tablets | 6.61 mm ± 0.2 mm | 6/Individual | 2 hours |
| Weight of 20 Tablets | 11.600 gm. ± 3% | 20/Composite | 30 minutes |
| Product Description | White color, elongated biconvex, uncoated tablet having one side mid break line and other side plain | 20/Composite | 2 hours |
| Uniformity of Weight | NMT 02 tablets out of 20 deviate from average weight by more than 3% and no single tablet deviates by more than 5% | 20/Composite | 01 hour |
| Average Weight of Tablets | 580 mg ± 2% | 20/Individual | 30 minutes |
| Hardness | NLT 4 kg/cm² | 6/Individual | 30 minutes |
| Disintegration Time | NMT 15 min | 6/Composite | 01 hour |
| Friability | NMT 1% | 20/Composite | 01 hour |
STEP – II: Send the sample of compressed tablets to QC department for analysis.
STEP – III: Weigh 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.
6.3 COATING
STEP – I (COATING MATERIALS DETAILS):
| Sr. No. | Material Name | Batch Quantity |
|---|---|---|
| 1 | Sheffcoat PVA Orange 5Y02059 | 4.350 kg |
| 2 | Purified water IP | 17.400 liter |
COATING EQUIPMENTS:
| Sr. No. | Machineries/Equipments | Capacity |
|---|---|---|
| 1 | Coating Pan | — |
| 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 with Nylon Filter Cloth 100# (0.5 mm). Keep the solution for 30 minutes and proceed for coating. Divide equally into two parts for LOT-I and LOT-II.
STEP – IV (COATING PROCEDURE) 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 tablets in coating pan (capacity: 42″), start hot air blower, set supply air temperature at 60° C to 65° C, warm tablet bed to 40° C to 45° C.
| Parameter | Specification | Status |
|---|---|---|
| No. of Baffles in coating pan | — | — |
| No. of Guns | — | — |
| Gun to Gun Distance | 08 inch | — |
| Gun to Tablet Bed Distance | 10 inch | — |
| BED Temperature | 40° C to 45° C | — |
| Pan RPM | 18 to 22 rpm | — |
| % Weight Gain | 2.0% | — |
STEP – V (COATING IN-PROCESS CHECK PARAMETERS): FOR LOT-I:
| Parameter | Standard | No. of Tablets | In-Process Frequency |
|---|---|---|---|
| Product Description | Orange color, elongated biconvex, film coated tablet having one side mid break line and other side plain | 20 No. | After batch completion |
| Weight of 20 Tablets after coating | 11.832 gm. ± 2% | 20 No. | — |
| Average Weight after coating | 591.6 mg ± 2% | 20 No. | — |
| Individual Tablets Weight Variation | — | 20 No. | — |
| Thickness | 6.63 mm ± 0.2 mm | — | — |
| Disintegration | NMT 30 min. | — | — |
FOR LOT – II: Please follow the same procedure of LOT – I of coating from Step-IV and Step-V.
STEP – VI: Send composite sample of coated tablets of LOT-I and LOT-II to QC department for analysis.
STEP – VII: Weigh the coated tablets and store into seven Poly-lined HDPE Containers with lid (capacity: 30 liter each) with proper status label till next step tablet packing.
