MFR of Pantoprazole Sodium 40 mg and Domperidone 10 mg Tablets in Pharma Industry
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 | ||
1.0 PRODUCT DETAILS:
| Product Name | Pantoprazole Sodium and Domperidone Tablets IP |
| Product Description | Off white color round biconvex shape, uncoated tablets having both side plain |
| Strength | Pantoprazole Sodium IP
equivalent to Pantoprazole 40 mg Domperidone IP 10 mg |
| Label claim
|
Each enteric coated tablet contains:
Pantoprazole Sodium IP equivalent to Pantoprazole – 40 mg Domperidone IP – 10 mg |
| Batch Size | 5,00,000 Tablets |
| Average Weight | 110 mg |
| Shelf Life | 24 months |
| Storage | Store in a cool, dry and dark place below 250C |
| Drug Category | Proton-Pump Inhibitors |
2.0 MANUFACTURING FORMULA:
| Material Name | Grade | Category | Quantity per Unit (In mg) | Overages | Batch Qty.
(In kg) without |
| Dry Mixing | |||||
| Pantoprazole Sodium
Equivalent to Pantoprazole |
IP | API | 40 mg | 13 % | 22.600 kg |
| Mannitol | IP | Diluent | 10 mg | —- | 5.000 kg |
| Sodium Carbonate | IP | Alkaline | 13 mg | —- | 6.500 kg |
| Dry Mixing (Part-II) | |||||
| Domperidone | IP | API | 10 mg | 1 % | 5.050 kg |
| MCCP-PH-102 | IP | Diluent | 3.2 mg | —- | 1.600 kg |
| Crospovidone XL | IP | Disintegrant | 6 mg | —- | 3.000 kg |
| Cross Carmillose Sodium | IP | Disintegrant | 10 mg | —- | 5.000 kg |
| Binder | |||||
| PVPK-30 | IP | Binder | 3 mg | —- | 1.500 kg |
| Isopropyl Alcohol (IPA) | IP | Diluent | 0.032 ml | —- | 16.000 liter |
| Lubricant | |||||
| Talcum | IP | Anti-caking agent | 3 mg | —- | 1.500 kg |
| Aerosil | IP | Glidant | 2.5 mg | —- | 1.250 kg |
| Calcium Stearate | IP | Anti-adherent | 4 mg | —- | 2.000 kg |
3.0 LIST OF EQUIPMENTS:
| Sr. No. | Machineries/equipments | Capacity | Equipment ID. |
| 1. | Weighing Balance | 100 kg | |
| 2. | Sifter | 30” | |
| 3. | Mass Mixer | 100 liter | |
| 4. | Stirrer for binder preparation | ||
| 5. | Tray Dryer | 48 Trays | |
| 6. | Multi-Mill (screen size 1.5 mm) | ||
| 7. | Double Cone Blender | 400 liter | |
| 8. | Halogen Moisture Balance | — | |
| 9. | Compression Machine | 35 Station | |
| 10. | SS Containers with lid | — | |
| 11. | Poly-lined HDPE Containers with lid | — |
4.0 MANUFACTURING INSTRUCTIONS:
Pantoprazole Sodium API Description: A white to off white powder.
Domperidone API Description: A white or almost white powder.
All the manufacturing activities shall be performed under controlled conditions
(temperature NMT 25 0C and relative humidity NMT 50%).
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.
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:
NOTE: Use Sodium Lamp and Black Poly-bags at every Step.
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 (Part-I) | ||
| Pantoprazole Sodium IP
equivalent to Pantoprazole |
22.600 kg | 40 # |
| Mannitol IP | 5.000 kg | 40 # |
| Sodium Carbonate IP | 6.500 kg | 100 # |
| Dry Mixing (Part-II) | ||
| Domperidone IP | 5.050 kg | 40 # |
| MCCP-PH-102 IP | 1.600 kg | 40 # |
| Crospovidone XL IP | 3.000 kg | 60 # |
| Cross Carmillose Sodium IP | 5.000 kg | 60 # |
| Binder | ||
| PVPK-30 IP | 1.500 kg | —- |
| Isopropyl Alcohol IP (IPA) | 16.00 liter | —- |
| Lubricant | ||
| Talcum IP | 1.500 kg | 60 # |
| Aerosil IP | 1.250 kg | 14 # |
| Calcium Stearate | 2.000 kg | 60 # |
NOT
Collect the sifted Pantoprazole Sodium IP (22.600 kg), Mannitol IP (5.000 kg)
and Sodium Carbonate (6.500 kg) into one Black Polybag (capacity : 50 kg)
Collect the sifted Domperidone IP (5.050 kg), MCCP-PH-102 IP (1.600 kg),
Crospovidone XL IP (3.000 kg) and Cross Carmillose Sodium IP (5.000 kg) in one
Black Polybag (capacity: 20 kg)
Collect the sifted Talcum IP (1.500 kg) and Aerosil IP (1.250 kg) in one
Black Polybag (capacity : 5.0 kg)
Collect the sifted Calcium Stearate IP (2.000 kg) in one Black Polybag (capacity: 5.0 kg)
STEP – II (DRY MIXING): PART-I:
Transfer the sifted Pantoprazole Sodium IP (22.600 kg) and Mannitol IP (5.000 kg)
and Sodium Carbonate (6.500 kg) in Mass Mixer (capacity: 100 liter).
(DRY MIXING): PART-II:
Transfer the sifted Domperidone IP (5.050 kg), MCCP-PH-102 IP (1.600 kg),
Crospovidone XL IP (3.000 kg) and Cross Carmillose Sodium IP (5.000 kg) in
Mass Mixer (capacity: 100 liter).
Mix together Part-I and Part-II of dry mixing material in Mass Mixer
(capacity: 100 liter) till uniform mixing.
Mixing Time: 10 minutes.
Mixing Speed: 36 RPM
Paddle (Blades) Timing & Direction: 5 minutes in clockwise direction &
5 minutes in anti-clockwise direction.
STEP – III (BINDER PREPARATION):
Take IPA (16.000 liter) in SS Container (capacity: 20 liter) and add PVPK-30 IP
(1.500 kg) and mix together with continuously stirring till dissolved properly in IPA.
Filter it with 100# filter cloth & store in SS Container (capacity: 20 liter).
STEP –IV (BINDING OF DRY MIX MATERIAL):
Slowly add the binder of Step-III in dry mix materials of Step-II and mix for
10 minutes till uniform binding and after binding, collect the wet mass into
seventeen Trays (capacity: 3.000 kg each).
Mixing Time: 10 minutes
Mixing Speed: 36 RPM
STEP –V (DRYING):
Dry the wet mass of Step -IV as follows:
First airs dry the granules for 30 minutes in Tray Dryer. Ensure that heaters are
in OFF mode. After air drying, Switch ON the heaters of Tray Dryer and set the
temperature at 35oC in Tray Dryer and dry the granules until the LOD of granules
is between 1.0 to 1.5% at 105oC checked by Halogen Moisture Balance.
Drying Time: 4 to 5 Hours.
Drying Temperature: 350C
Raking Frequency: After every 15 minutes
STEP-VI (SIZING/MILLING):
Check Screen Integrity (before sifting and after sifting).
Milled the dried material of Step -V through Multi Mill using screen size 1.5 mm
and collect milled material in two 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
STEP – VII (PRE –LUBRICATION):
Load the milled granules of Step-VI in Double Cone Blender (capacity : 400 liter)
and add sifted Talcum IP (1.500 kg) and Aerosil IP (1.250 kg) and mix properly till
uniform mixing of milled material with Pre-Lubricating Material.
Mixing Time: 30 minutes (15 minutes clockwise direction and 15 minutes anti-clockwise direction)
Mixing Speed: 10 RPM
STEP – VIII (LUBRICATION):
Add the sifted Calcium Stearate IP (2.000 kg) in Pre- Lubricated Material of Step-VII
and mix properly till uniform mixing of materials with Calcium Stearate IP.
Mixing Time: 05 minutes. (clockwise direction)
Mixing Speed: 10 RPM.
STEP- IX (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
|
Off white free flowing granular powder
90 % to 110 % 98 % to 103 % 1.0 % to 1.5 % To be established in next batch To be established in next batch To be established in next batch To be established in next batch |
STEP – X:
Unload the above blended material and weight and store into two Poly-lined HDPE
Container (capacity: 30 liter each)
STEP – XI:
Clean all equipments 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 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
|
5 -6 Tones (B-Tooling, 35 station Compression Machine) | —– | —– |
| 4. | Machine Speed | 20 RPM -22 RPM | —– | —– |
| 5. | Upper Punch Size | 6.5 mm | —– | —– |
| 6. | Lower Punch Size | 6.5 mm | —– | —– |
| 7. | Die | 6.5 mm | ||
| 8. | Diameter | 6.5 mm | 6/Individual | 2 hours |
| 9. | Thickness of Tablets | 2.70 mm ±.2 mm | 6/Individual | 2 hours |
| 10. | Weight of 20 Tablets | 2.200 gm. ± 2% | 20/Composite | 30 minutes |
| 11. | Tablets for Dissolution | 2.200 gm. ± 2% | ||
| 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 | 110 mg ± 2 % | 20/Individual | 30 minutes |
| 14. | Hardness | NLT 2.5 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:
Weigh the compressed tablets and store into two Poly-lined HDPE Containers
(capacity: 30 liter each) with proper status label till next step tablet coating.
STEP – IV:
Clean the Compression Machine as per cleaning SOP