Terms and Conditions

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

Byiamraj

Feb 25, 2021 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

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.

 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 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 condition. 

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

 

By iamraj