Drugsformulations
MFR of Telmisartan 40 mg Tablets IP
TABLE OF CONTENTS
| S.NO. | TITLE | |
| 1.0 | PRODUCT DETAILS | |
| 2.0 | MANUFACTURING FORMULA | |
| 3.0 | LIST OF EQUIPMENTS | |
| 4.0 | GENERAL PRECAUTIONS | |
| 5.0 | MANUFACTURING INSTRUCTIONS | |
| 6.0
| MANUFACTURING PROCESS DETAILS | |
| 6.1 | GRANULATION | |
| 6.2 | COMPRESSION | |
| 6.3 | COATING | |
| 6.4 | BRAND DETAILS | |
1.0 PRODUCT DETAILS:
| Product Name | Telmisartan 40 mg Tablets IP |
| Product Description | White color, round shape, biconvex, film coated tablet having plain on both sides. |
| Strength | Telmisartan 40 mg |
| Label claim
| Each film coated tablet contains: Telmisartan IP – 40 mg |
| Batch Size | 4,00,000 Tablets |
| Average Weight | 220 mg (Uncoated tablets) 224.400 mg (Film coated tablets) |
| Shelf Life | 24 months |
| Storage | Store in a cool, dry and dark place below 25 0C |
| Drug Category | Anti-hypertensive |
2.0 MANUFACTURING FORMULA:
| Material Name | Grade | Category | Quantity per Unit (In mg) | Overages | Batch Qty. (In kg) |
| Slurry Preparation | |||||
| Telmisartan | IP | API | 40.00 mg | — | 16.000 kg |
| Tween 80 | IP | Solubilizing agent | 3.00 mg | — | 1.200 kg |
| Sodium Hydroxide (Flakes) | IP | pH adjuster | 4.00 mg | — | 1.600 kg |
| Purified Water | IP | Solvent | 0.0692 ml | 27.680 liter | |
| Dry Mixing | |||||
| MCCP-102 | IP | Diluent | 100.00 mg | — | 40.000 kg |
| Lubricant | |||||
| Talcum | IP | Anti caking agent | 2.00 mg | — | 0.800 kg |
| MCCP-102 | IP | Diluent | 18.50 mg | — | 7.400 kg |
| Sodium Starch Glycolate | IP | Disintegrants | 7.50 mg | — | 3.000 kg |
| Crospovidone XL-10 | IP | Disintegrant | 30.00 mg | — | 12.000 kg |
| Cross Carmel lose Sodium | IP | Disintegrants | 15.00 mg | — | 6.000 kg |
3.0 LIST OF EQUIPMENTS:
| Sr.No. | Machineries/Equipments | Capacity |
| 1. | Weighing Balance | 100 kg |
| 2. | Vibro Sifter (with SS Sieves No’s 30, 40 and 60 ) | 30 inch dia |
| 3. | Mass Mixer with Propeller | 100 liter |
| 4. | Paste Kettle | 100 liter |
| 5. | Planetary Mixer | 100 liter |
| 6. | Tray Dryer | 48 Trays |
| 7. | Multi Mill (screen size 1.5 mm) | — |
| 8. | Double Cone Blender | 200 liter |
| 9. | Halogen Moisture Balance | — |
| 10. | Compression Machine | 35 Station |
| 11. | SS Containers with lid | 10 liter (01 No.) 70 liter (01 No.) 100 liter (01 No.) |
| 12. | Poly-lined HDPE Containers | 45 liter (08 No’s) |
| 13. | Polybag | 20 kg (03 No’s) 50 kg (01 No.) |
4.0 GENERAL PRECAUTIONS:
- API Description: A white to off 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
- MANUFACTURING INSTRUCTIONS:
- All the Activity shall be performed as per current SOPs.
- Take the line clearance from QA before starting the manufacturing operation during batch to batch
and product to product change over.
- Do not overwrite any entry. In case of mistake, 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 Vibro Sifter (capacity: 30 inch dia) and sieve the Dispensed Materials as per Sieve Sizes mentioned below:
| Material Name | Std. Qty. (kg) | Sieve No. |
| Slurry Preparation | ||
| Telmisartan IP | 16.000 kg | 30 # |
| Tween 80 IP | 1.200 kg | – |
| Sodium Hydroxide(Flakes) IP | 1.600 kg | – |
| Dry Mixing | ||
| MCCP PH-102 IP | 40.000 kg | 40# |
| Lubricants | ||
| Talcum IP | 0.800 kg | 60# |
| MCCP PH-102 IP | 7.400 kg | 40# |
| Sodium Starch Glycolate IP | 3.000 kg | 60# |
| Crospovidone XL IP | 12.000 kg | 40# |
| Cross Carmellose Sodium IP | 6.000 kg | 40# |
- Collect sifted MCCP PH 102 IP (40.000 kg) in one Polybag (capacity: 50 kg).
- Collect sifted Telmisartan IP (16.000 kg) in one Polybag (capacity: 20 kg).
- Collect sifted Talcum IP (0.800 kg), MCCP PH-102 IP (7.400 kg), Sodium Starch Glycolate IP (3.000 kg), Crospovidone XL IP (12.000 kg) and Cross Carmellose Sodium IP (6.000 kg) in two Polybags (capacity: 20 kg each)
STEP – II (SLURRY PREPARATION):
- Take purified water (24.480 liter) in Paste Kettle (capacity: 100 liter), heated the purified water to 450
- Transfer the heated purified water (Qty. 24.480 liter) of Step-II (a) in Planetary Mixer (capacity: 100 liter) and add Tween-80 IP (1.200 kg) in it. Mix properly with continuously stirring until the consistent slurry appears.
- Slowly-slowly add Telmisartan IP in Step-II (b) with continuously stirring until the consistent slurry appears.
- Take purified water at room temperature separately (3.200 liter) in SS Container (capacity: 10 liter) and add Sodium Hydroxide (flakes) IP and mix properly with continuously stirring till dissolved properly in water.
- Let the solution of Step-II (d) cool down, solution become warm due to exothermic reaction therefore hold the solution for half an hour.
- Add the solution of Step-II (e) drop wise in Step-II(c) continuously stirring, until the color of solution becomes like honey and all lumps in slurry disappear.
- Transfer the ready slurry by tilting the Planetary Mixer in one SS Container (capacity: 70 liter).
STEP – III (BINDING OF DRY MIX MATERIAL):
Transfer the sifted material MCCP-102 IP (40.000 kg) in Mass Mixer, (capacity 100 liter) and dry mix the material. Slowly add the slurry of Step-II (g) in it and mix for 20 minutes till uniform binding and after binding , collect the wet mass in SS Container (capacity: 100 liter).
Mixing time: 20 minutes (To be validated in next batch)
Mixing Speed: 36 RPM.
Paddle (Blades) Timing: 10 minutes in clockwise direction and 10 minutes in anti – clockwise direction.
STEP-V (WET SCREENING):
Check Sieve Integrity (before and after screening).
Take the wet material from SS Container and pass through sieve size 30 # manually and collect the wet material after sieving in SS thirty trays ( capacity: 3.000 kg each).
STEP – VI (DRYING):
Dry the wet materials of Step – V as follow:
Load these thirty Trays in Tray Dryer.
Switch ON the heaters and set the temperature at 45°C of Tray Dryer and dry the granules, until the LOD of granules is achieved between 1.0 % at 105°C checking by Halogen Moisture Balance.
Drying Time: 10 hours (To be validated in next batch)
Drying Temperature: 45°C
Raking Frequency: After every 30 minutes.
STEP – VII (SIZING /MILLING):
Check Sieve & Screen Integrity (before and after sifting & screening).
Set the Vibro Sifter and fix the Sieve 30 # and sieve the dried material of Step-VI and collect in two Poly-lined HDPE Containers (capacity: 45 liter each) and remaining retention after sieving, pass through the Multi-Mill using screen size 1.5 mm. After screening keep the screened material with sized material in above Poly-lined HDPE Containers. Weigh and record the sized/milled granules quantity.
Blade Type: Both (Knife blades and Scraping blades).
Rotor Speed: 2000 RPM.
STEP – VIII (LUBRICATION):
Load the sized granules of Step-VII in Double Cone Blender (capacity: 200 liter) and add sifted Talcum IP, MCCP PH-102. Sodium Starch Glycolate IP, Crospovidone XL IP and Cross Carmellose Sodium and mix properly till uniform mixing of sized granules with Lubricating Materials.
Mixing Time: 30 minutes (15 minutes clockwise direction and 15 minutes anti-clockwise direction)
Mixing Speed: 10 RPM
STEP- IX (BLEND SAMPLE ANALYSIS)
- After completion of lubrication, collect the composite blend sample (Qty: 10 gm) 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 to off-white free flowing granular powder 90 % to 110 % 98 % to 103 % 1.0 % 0.525 gm/ml 0.700 gm/ml 24.561 % 1.3256 |
STEP – X:
- Take Tare Weight of three Poly-lined HDPE Containers (capacity: 45 liter each), record the Tare Weight in BMR and unload the above blended material from Double Cone Blender in Poly-lined HDPE Containers (capacity: 45 liter each) and weigh the material with containers and record the Gross Weight of the material and calculate the Net Weight of the material as per given formula:
Net Weight = Gross Weight – Tare weight
- Affix the status label with following details – Product Name, Batch No., Batch Size, Mfg. Date, Exp. Date, Tare Weight, Gross Weight and Net Weight on the Poly-lined HDPE Containers.
- Batch Yield of Lubricated granules:
Theoretical Batch Yield: 88.00 kg (100 %)
Actual Batch Yield Limit NLT 87.120 kg (NLT 99 %) (To be established in next batch)
STEP – XI:
- Clean all equipments used in the granulation as per respective equipment cleaning SOP.
6.2 COMPRESSION:
STEP – I:
- After receiving of QC approval for the blend, verify the Net Weight of the received blend as per status label in Granules Day Store.
- Set the 35 stations (B-Tooling) Compression Machine. Compress the blend as per below parameters and In Process checks and take a sample for Dissolution (Qty. 20 tablets) and send to QC Department for Dissolution Analysis.
- After confirmation of Dissolution result continue the compression with the blend as per the following parameters and In Process checks under controlled environmental conditions.
| 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 | —– | —– |
| 4. | Machine Speed | 15RPM to 18 RPM | —– | —– |
| 5. | Common Name of Die | Himosin | ||
| 6. | Upper Punch Size | 9.50 mm | —– | —– |
| 7. | Lower Punch Size | 9.50 mm | —– | —– |
| 8. | Diameter of Tablet | 9.50 mm | 6/Individual | 2 hours |
| 9. | Thickness of Tablets | 3.20 mm ± 0.2 mm | 6/Individual | 2 hours |
| 10. | Weight of 20 Tablets | 4.400 gm. ± 2 % | 20/Composite | 30 minutes |
| 11. | Tablets for Dissolution | 4.400 gm. ± 2 % | 20/Composite | Before starting the Compression |
| 12. | Dissolution | NLT 80 % | —- | —- |
| 13. | Product Description | Off white, round shape, biconvex, uncoated tablet having both side plain | 20/Composite | 30 minutes |
| 14. | Uniformity of Weight | NMT 02 tablets out of 20 deviate from the standard average weight by more than 3 % and no single tablet deviates from the standard average weight by more than 5 % | —– | 01 hour |
| 15. | Standard Average Weight of Tablets | 220 mg ± 2 % | 20/Individual | 30 minutes |
| 16. | Hardness | NLT 3 kg/cm2 | 6/Individual | 30 minutes |
| 17. | Disintegration Time | NMT 15 min | 6/Composite | 01 hour |
| 18. | Friability | NMT 1% | 20/Composite | 01 hour |
- Collect the compressed tablets in SS Container (capacity: 20 liter each on both sides), when SS containers are filled with tablets, transfer the tablets in three Poly-lined HDPE Containers as given in below Step-III.
STEP – II:
- Send the composite sample of compressed tablets (Qty. 30 tablets) to QC department for analysis.
STEP – III:
- Take Tare Weight of three Poly-lined HDPE Containers (capacity: 45 liter each), record the Tare Weight in BMR and transfer the compressed tablets in Poly-lined HDPE Containers (capacity: 45 liter each) and weigh the compressed tablets with containers and record the Gross Weight of the compressed tablets and calculate the Net Weight of the material as per given formula:
Net Weight = Gross Weight – Tare weight
- Affix the status label with following details – Product Name, Batch No., Batch Size, Avg. Weight Mfg. Date, Exp. Date, Tare Weight, Gross Weight and Net Weight on the Poly-lined HDPE Container.
- Batch Yield of Compressed Tablets:
Theoretical Batch Yield: 88.00 kg (100 %)
Actual Batch Yield Limit NLT 87.120 kg (NLT 99 %) (To be established in next batch)
STEP – IV:
- After completion of compression of the tablets, clean the Compression Machine as per cleaning SOP.
6.3 COATING:
- Verify the Net Weight of the received compressed tablets for coating as per status label and after confirmation continue for tablet coating.
| Sr. No. | Material Name | Batch Quantity |
| 1. | Instacoat White Aq. III | 1.760 kg |
| 2. | Purified Water IP | 10.560 liter |
NOTE:
Color: As per packing material /according to the brands/products. The color and quantity of color to be used may vary from product to product as per the reference sample.
STEP-II (LIST OF EQUIPMENTS FOR COATING):
| Sr. No. | Machineries/Equipments | Capacity |
| 1. | Coating Pan & Coating Machine | 42″ |
| 2. | Spray Gun | 02 |
| 3. | Filter Cloth 100 # | 0.5 meter |
| 4. | Portable Stirrer | — |
| 5. | SS Containers | 20 liter (02 No’s) |
| 6. | Poly-lined HDPE Containers with lid | 45 liter (03 No’s) |
STEP – III (PREPARATION OF COATING SOLUTION):
- Take Purified Water IP (10.560 liter, at room temperature) in SS Container (capacity: 20 liter) and add Instacoat White Aq.III (1.760 kg), mix together by Portable Stirrer properly continuously stirring till uniform mixing achieved.
Mixing Time: 15 minutes. (To be validated in next batch)
Speed of stirrer: Constant.
- Filter the coating solution with Filter Cloth 100 # in SS Container (capacity: 20 liter)
- Keep the solution for 15 minutes to let the foam settle down. Thereafter proceed with coating process.
STEP – IV (COATING PROCEDURE):
- Coating will be done in one lot, take total compressed tablets (88.000 kg tablets) for coating.
- Load the tablets in coating pan (capacity: 42″), start the hot air blower, set the inlet air temperature at 70°C to 75°C and start the exhaust fan & warm the tablets bed 40°C to 45°C
- After warming up the tablets, take weight of 100 warmed tablets and also take weight of 100 tablets after coating record the weight in BMR 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 through gun.
- After completion of coating, calculated the weight gain by using Formula of weight gain in below table.
| Parameter | Specification |
| No. of Baffles in coating pan | 03 |
| No. of Guns | 01 |
| Inlet Temperature | 70°C to 75°C |
| Peristaltic Pump Speed | 2 – 4 RPM (To be validated in next batch) |
| Atomization | 2.5 to 3.0 kg/cm2 |
| Gun to Tablet Bed Distance | 8 inch |
| BED Temperature | 400C to 45 0C (To be validated in next batch) |
| Pan RPM | 13 to 15 RPM |
| % Weight Gain (1.5 to 2.0 %) | Weight of Film Coated Tablets – Weight of Uncoated Tablets x 100/ Weight of Film Coated Tablets |
| Coating Time | 02 Hours (To be validated in next batch) |
STEP – V (COATING IN-PROCESS CHECK PARAMETERS):
| S.No. | Parameters | Standard | No. of Tablets | In-Process Frequency |
| 1 | Product Description | White color, round shape, biconvex, film coated tablet having both side plain | 20 No. |
After batch completion |
| 2 | Weight of 20 Tablets after coating | 4.488 gm.( 2 % Weight Gain) | 20 No. | |
| 3 | Average Weight after coating | 224.4 mg (2% Weight Gain) | 20 No. | |
| 4 | Individual Tablets Weight Variation | NMT 02 tablets out of 20 deviate from the standard average weight by more than 3 % and no single tablet deviates from the standard average weight by more than 5 % | 20 No. | |
| 5 | Thickness | 2.81 mm ± 0.2 mm | 6 No. | |
| 6 | Disintegration | NMT 30 min. | 6 No. |
STEP – VI:
- Send the composite sample of coated tablets (Qty. 30 tablets) to QC department for analysis.
STEP – VII:
- Take Tare Weight of three Poly-lined HDPE Containers (capacity: 45 liter each), record the Tare Weight in BMR and transfer the coated tablets in Poly-lined HDPE Containers (capacity: 45 liter each) and weigh the coated tablets with containers and record the Gross Weight of the coated tablets and calculate the Net Weight of the material as per given formula:
Net Weight = Gross Weight – Tare weight
- Affix the status label with following details – Product Name, Batch No., Batch Size, Avg. Weight, Mfg. Date, Exp. Date, Tare Weight, Gross Weight and Net Weight on the Poly-lined HDPE Containers.
- Batch Yield of Coated Tablets:
Theoretical Batch Yield: 89.760 kg (100 %)
Actual Batch Yield Limit NLT 88.862 kg (NLT 99 %) (To be established in next batch).
