Telmisartan 40 mg Tablets IP
TABLE OF CONTENTS
- PRODUCT DETAILS
- MANUFACTURING FORMULA
- LIST OF EQUIPMENT
- GENERAL PRECAUTIONS
- MANUFACTURING INSTRUCTIONS
- MANUFACTURING PROCESS DETAILS -GRANULATION, COMPRESSION,COATING, BRAND DETAILS,
PRODUCT DETAILS:
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
Drug Category:Anti-hypertensive
Storage: Store in a cool, dry, and dark place below 25 0C
Shelf Life:24 months
Average Weight:225 mg
MANUFACTURING FORMULA:
| Material Name | Grade | Category |
| Slurry Preparation | ||
| Telmisartan | IP | API |
| Tween 80 | IP | Solubilizing agent |
| Sodium Hydroxide (Flakes) | IP | pH adjuster |
| Purified Water | IP | Solvent |
| Dry Mixing | ||
| MCCP-102 | IP | Diluent |
| Lubricant | ||
| Talcum | IP | Anti-caking agent |
| MCCP-102 | IP | Diluent |
| Sodium Starch Glycolate | IP | Disintegrants |
| Crospovidone XL-10 | IP | Disintegrant |
| Cross Carmellose Sodium | IP | Disintegrants |
Machinery/Equipment
- Weighing Balance
- Vibro Sifter
- Mass Mixer with Propeller
- Paste Kettle
- Planetary Mixer
- Tray Dryer
- Multi Mill (screen size 1.5 mm)
- Double Cone Blender
- Halogen Moisture Balance
- Compression Machine
- SS Containers with lid
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 products or a mixture of Active Ingredients and Excipients, wear gloves and a mask to avoid exposure and contact with any body parts
MANUFACTURING INSTRUCTIONS:
All the Activities 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:
GRANULATION:
STEP – I (SIFTING):
Check Sieve Integrity (before sifting and after sifting).
Set the Vibro Sifter 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.
- Collect sifted Telmisartan IP (16.000 kg) in one Polybag.
- 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.
STEP – II (SLURRY PREPARATION):
- Take purified water (24.480 liters) in Paste Kettle, heated the purified water to 450
- Transfer the heated purified water (Qty. 24.480 liters) of Step-II (a) to Planetary Mixer and add Tween-80 IP (1.200 kg) to it. Mix properly with continuous stirring until the consistent slurry appears.
- Slowly-slowly add Telmisartan IP in Step-II (b) with continuous stirring until the consistent slurry appears.
- Take purified water at room temperature separately (3.200 liters) in SS Container and add Sodium Hydroxide (flakes) IP and mix properly with continuous stirring till dissolved properly in water.
- Let the solution of Step-II (d) cool down, the solution becomes warm due to an exothermic reaction, therefore, holding the solution for half an hour.
- Add the solution of Step-II (e) dropwise in Step-II(c) continuously stirring, until the color of the solution becomes like honey and all lumps in the slurry disappear.
- Transfer the ready slurry by tilting the Planetary Mixer in one SS Container.
STEP – III (BINDING OF DRY MIX MATERIAL):
Transfer the sifted material MCCP-102 IP (40.000 kg) to Mass Mixer and dry mix the material. Slowly add the slurry of Step-II (g) in it and mix for 20 minutes till uniform binding after binding, collect the wet mass in SS Container.
Mixing time: 20 minutes
Mixing Speed: 36 RPM.
Paddle (Blades) Timing: 10 minutes in a 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 it through sieve size 30 # manually and collect the wet material after sieving in SS thirty trays.
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.
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 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 the 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 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
The appearance of blend: White to an off-white free-flowing granular powder.
Blend Uniformity:90 % to 110 %
Blend Assay:98 % to 103 %
LOD:1.0 %
For Informative tests – Bulk Density, Tapped Density, Compressibility Index, Hausner Ratio
STEP – X:
- Take Tare Weight of three Poly-lined HDPE Containers, record the Tare Weight in BMR and unload the above-blended material from Double Cone Blender in Poly-lined HDPE Containers 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 the 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 equipment used in the granulation as per respective equipment cleaning SOP.
COMPRESSION:
STEP – I:
After receiving QC approval for the blend, verify the Net Weight of the received blend as per the status label in Granules Day Store.
Set the 35 stations (B-Tooling) Compression Machine. Compress the blend as per the below parameters and In Process checks and take a sample for Dissolution (Qty. 20 tablets) and send it to QC Department for Dissolution Analysis.
After confirmation of the Dissolution result continues the compression with the blend as per the following parameters and In Process checks under controlled environmental conditions.
| Parameters | Standard | No. of Tablets | In-Process Frequency |
| Machine Speed | 15RPM to 18 RPM | —– | —– |
| Diameter of Tablet | 9.50 mm | 6/Individual | 2 hours |
| Thickness of Tablets | 3.20 mm ± 0.2 mm | 6/Individual | 2 hours |
| Weight of 20 Tablets | 4.400 gm. ± 2 % | 20/Composite | 30 minutes |
| Tablets for Dissolution | 4.400 gm. ± 2 % | 20/Composite | Before starting the Compression |
| Dissolution | NLT 80 % | —- | —- |
| Product Description | Off-white, round shape, biconvex, uncoated tablet having both side plain | 20/Composite | 30 minutes |
| 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 |
| Standard Average Weight of Tablets | 220 mg ± 2 % | 20/Individual | 30 minutes |
| Hardness | NLT 3 kg/cm2 | 6/Individual | 30 minutes |
| Disintegration Time | NMT 15 min | 6/Composite | 01 hour |
| Friability | NMT 1% | 20/Composite | 01 hour |
Collect the compressed tablets in SS Container, when SS containers are filled with tablets, transfer the tablets to three Poly-lined HDPE Containers as given in below Step-III.
STEP – II:
Send the composite sample of compressed tablets (Qty. 30 tablets) to the QC department for analysis.
STEP – III:
Take Tare Weight of three Poly-lined HDPE Containers, record the Tare Weight in BMR and transfer the compressed tablets 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 the given formula:
Net Weight = Gross Weight – Tare weight
Affix the status label with the 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.
COATING:
Verify the Net Weight of the received compressed tablets for coating as per the status label and after confirmation continues for tablet coating.
| Material Name | Batch Quantity |
| Instagram White Aq. III | 1.760 kg |
| Purified Water IP | 10.560 liter |
STEP-II (LIST OF EQUIPMENT FOR COATING):
Machinery/Equipment
Coating Pan & Coating Machine
Spray Gun
Filter Cloth 100 #
Portable Stirrer
SS Containers
STEP – III (PREPARATION OF COATING SOLUTION):
Take Purified Water IP, at room temperature) in SS Container and add Instacoat White Aq.III (1.760 kg), mix together with Portable Stirrer properly continuously stirring till uniform mixing is achieved.
Mixing Time: 15 minutes.
Speed of stirrer: Constant.
Filter the coating solution with Filter Cloth 100 # in SS Container (capacity: 20 liters)
Keep the solution for 15 minutes to let the foam settle down. Thereafter proceed with the 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 a coating pan, 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 from 40°C to 45°C
After warming up the tablets, take the weight of 100 warmed tablets and also take the weight of 100 tablets after coating record the weight in BMR for calculation of the weight buildup of tablets after coating.
Set the coating parameter as given in the below table and start the coating process by starting the coating spray through gun.
After completion of coating, calculated the weight gain by using the Formula of weight gain in the below table.
Parameter/Specification
Inlet Temperature:70°C to 75°C
Peristaltic Pump Speed:2 – 4 RPM
Atomization:2.5 to 3.0 kg/cm2
Gun to Tablet Bed Distance:8 inch
BED Temperature:400C to 45 0C
Pan RPM:13 to 15 RPM
% Weight Gain (1.5 to 2.0 %)
Coating Time:02 Hours
Weight of Film Coated Tablets – Weight of Uncoated Tablets x 100/ Weight of Film Coated Tablets
STEP – V (COATING IN-PROCESS CHECK PARAMETERS):
| Parameters | Standard | In-Process Frequency |
| Product Description | White color, round shape, biconvex, film-coated tablet having both side plain |
After batch completion |
| Weight of 20 Tablets after coating | 4.488 gm.( 2 % Weight Gain) | |
| Average Weight after coating | 224.4 mg (2% Weight Gain) | |
| 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 % | |
| Thickness | 2.81 mm ± 0.2 mm | |
| Disintegration | NMT 30 min. |
STEP – VI:
- Send the composite sample of coated tablets to the QC department for analysis.
STEP – VII:
- Take Tare Weight of three Poly-lined HDPE Containers, record the Tare Weight in BMR and transfer the coated tablets to Poly-lined HDPE Containers 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 the 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).