MFR of Pantoprazole Sodium 40 mg and Domperidone 10 mg Tablets in Pharma Industry

MFR of Pantoprazole Sodium 40 mg and Domperidone 10 mg Tablets in Pharma Industry 

TABLE OF CONTENTS 

S.NO.TITLEPage No
1.0PRODUCT DETAILS
2.0MANUFACTURING FORMULA
3.0LIST OF EQUIPMENTS
4.0MANUFACTURING INSTRUCTIONS
5.0GENERAL PRECAUTIONS
6.0

 

 

 

MANUFACTURING PROCESS DETAILS
6.1GRANULATION
6.2COMPRESSION

1.0 PRODUCT DETAILS:

Product NamePantoprazole Sodium and Domperidone Tablets IP
Product DescriptionOff white color round biconvex shape, uncoated tablets having both side plain
StrengthPantoprazole 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 Size5,00,000 Tablets
Average Weight110 mg
Shelf Life24 months
StorageStore in a cool, dry and dark place below 250C
Drug CategoryProton-Pump Inhibitors

2.0 MANUFACTURING FORMULA:

Material NameGradeCategoryQuantity per Unit (In mg)OveragesBatch Qty.

 (In kg) without

Dry Mixing     
Pantoprazole Sodium

Equivalent to Pantoprazole

 IPAPI40  mg13 %22.600 kg
MannitolIPDiluent 10 mg—-5.000 kg
Sodium CarbonateIPAlkaline 13  mg—-6.500 kg
Dry Mixing (Part-II)
DomperidoneIPAPI10 mg1 %5.050 kg
MCCP-PH-102IPDiluent3.2 mg—-1.600 kg
Crospovidone XLIPDisintegrant6 mg—-3.000 kg
Cross Carmillose SodiumIPDisintegrant10 mg—-5.000 kg
Binder
PVPK-30IPBinder3 mg—-1.500 kg
Isopropyl Alcohol (IPA)IPDiluent0.032 ml—-16.000 liter
Lubricant
TalcumIPAnti-caking agent3 mg—-1.500 kg
AerosilIPGlidant2.5 mg—-1.250 kg
Calcium StearateIPAnti-adherent4 mg—-2.000 kg

3.0 LIST OF EQUIPMENTS:                         

Sr. No.Machineries/equipmentsCapacityEquipment ID.
1.Weighing Balance100 kg
2.Sifter30”
3.Mass Mixer100 liter
4.Stirrer for binder preparation
5.Tray Dryer48 Trays
6.Multi-Mill (screen size 1.5 mm)
7.Double Cone Blender400 liter
8.Halogen Moisture Balance
9.Compression Machine35 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.

 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 (Part-I)
Pantoprazole Sodium IP

equivalent to Pantoprazole

22.600 kg40 #
Mannitol IP5.000 kg40 #
Sodium Carbonate IP6.500 kg100 #
Dry Mixing (Part-II)
Domperidone IP5.050 kg40 #
MCCP-PH-102 IP1.600 kg40 #
Crospovidone XL IP3.000 kg60 #
Cross Carmillose Sodium IP5.000 kg60 #
Binder
PVPK-30 IP1.500 kg—-
Isopropyl Alcohol IP (IPA)16.00 liter—-
Lubricant
Talcum IP1.500 kg60 #
Aerosil IP1.250 kg14 #
Calcium Stearate2.000  kg60 #

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:

TestSpecification
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 condition. 

S.

No.

ParametersStandardNo. of TabletsIn-Process Frequency
1.       Feed frame alignment and adjustmentShould be satisfactory—–—–
2.       Lower Weight AssemblyShould be satisfactory—–—–
3.       Hydraulic Pressure

 

5 -6 Tones (B-Tooling, 35 station Compression Machine)—–—–
4.       Machine Speed20 RPM -22 RPM—–—–
5.       Upper Punch Size6.5  mm­—–—–
6.       Lower Punch Size6.5  mm—–—–
7.       Die6.5 mm
8.        Diameter6.5 mm6/Individual2 hours
9.       Thickness of Tablets2.70 mm ±.2 mm6/Individual2 hours
10.   Weight of 20 Tablets2.200 gm. ± 2%20/Composite30 minutes
11.   Tablets for Dissolution2.200 gm. ± 2%
12.   Uniformity of WeightNMT 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 Tablets110 mg ± 2 %20/Individual30 minutes
14.   HardnessNLT 2.5 kg/cm26/Individual30 minutes
15.   Disintegration TimeNMT 15 min6/Composite01 hour
16.   FriabilityNMT 1%20/Composite01 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