MFR of Pantoprazole Sodium 40 mg Tablets IP

TABLE OF CONTENTS

 

S.NO. TITLE Page No
1.0 PRODUCT DETAILS 2 of 11
2.0 MANUFACTURING FORMULA 2 of 11
3.0 LIST OF EQUIPMENTS 2 of 11

 

4.0 GENERAL PRECAUTIONS 3 of 11
5.0 MANUFACTURING INSTRUCTIONS 3 of 11
6.0

 

 

 

MANUFACTURING PROCESS DETAILS
6.1 GRANULATION 3 of 11
6.2 COMPRESSION 6 of 11
6.3  COATING 7 of 11
6.4  BRAND DETAILS 11 of 11

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1.0 PRODUCT DETAILS:

Product Name Pantoprazole Sodium Tablets IP
Product Description Yellow color, round shape, biconvex, enteric coated tablets having both side plain
Strength  Pantoprazole Sodium  – 40 mg
Label claim

 

Each enteric coated tablet contains:

Pantoprazole Sodium IP

equivalent to Pantoprazole  40 mg

Batch Size 5,00,000 Tablets
Average Weight 110 mg (Uncoated tablets)

121 mg (Enteric coated tablets)

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)

Dry Mixing
Pantoprazole Sodium  IP API 40  mg 13 % 22.600 kg
Mannitol IP Diluent   32 mg —- 16.000 kg
Cross Carmellose Sodium IP Disintegrant 3.5 mg 1.750 kg
Sodium Carbonate IP Alkaline 8 mg 4.000 kg
Binder
PVPK-30 IP Binder 2.5 mg —- 1.250 kg
Isopropyl Alcohol (IPA) IP Solvent 0.047 ml —- 23.500 liter
Lubricant
Talcum IP Anti-caking agent 2.8 mg —- 1.400 kg
Cross Carmellose Sodium IP Disintegrant 3.5 mg —- 1.750 kg
Crospovidone XL IP Disintegrant 5 mg —- 2.500 kg
Aerosil IP Glidant 2.5 mg —- 1.250 kg
Calcium Stearate IP Anti-adherent 5 mg —- 2.500 kg

3.0 LIST OF EQUIPMENTS:                         

 Sr. No. Machineries/Equipments Capacity Equipment ID.
1. Weighing Balance 100 kg SC/PD/WBL/03
2. Vibro Sifter

(with SS Sieves  No’s 14,20, 40, 60,80)

30 inch dia SC/PD/SFT/01

SC/PD/SFT/02

3. Mass Mixer with propeller 100 liter SC/PD/MSM/01,SC/PD/MSM/02
4. Portable Stirrer SC/PD/STR/01,SC/PD/STR/02
5. Tray Dryer 48 Trays SC/PD/TRD/01,SC/PD/TRD/02

SC/PD/TRD/03,SC/PD/TRD/04

6. Double Cone Blender 200 liter SC/PD/DCB/01
7. Halogen Moisture Balance SC/QC/007
8. Compression Machine 35 Station SC/PD/CPM/02,SC/PD/CPM/06
9. SS Containers 30 liter (02 No’s)
10. Poly-lined HDPE Containers with lid 30 liter (08 No’s)
11. Polybags 2 kg (01 No.),

5 kg (01 No.),

10 kg (01 No.)

12. Filter Cloth 100 # 0.5 Meter

4.0 GENERAL PRECAUTIONS:

  • API Description: A white to off white powder.(Light Sensitive)
  • 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.
  • Use Sodium Lamp and Black Poly-bags at every Step.
  • MANUFACTURING INSTRUCTIONS:
  • All the Activity shall be performed as per current SOPs.
  • Take the line clearance of every machine 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.

6.0 MANUFACTURING PROCESS DETAILS:

6.1 GRANULATION:

   NOTE: Turn ON the sodium lamp and switch OFF all lights before starting the operation and use black polybags to store the materials.

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.
Dry Mixing
Pantoprazole Sodium IP

 

22.600 kg 40 #
Mannitol IP 16.000 kg 40 #
Cross Carmellose Sodium IP 1.750 kg 60 #
Sodium Carbonate IP 4.000 kg 80 #
Binder
PVPK-30 IP 1.250 kg 20 #
Isopropyl Alcohol IP (IPA) 23.500 liter NA
Lubricant
Talcum IP 1.400 kg 60 #
Cross Carmellose Sodium IP 1.750 kg 60 #
Crospovidone XL 2.500 kg 60 #
Aerosil IP 1.250 kg 14 #
Calcium Stearate 2.500 kg 60 #

NOT

  • Collect sifted Pantoprazole Sodium IP (22.600 kg), Mannitol IP (16.000 kg), Cross Carmellose Sodium IP (1.750 kg) and Sodium Carbonate (4.000 kg) into two Poly-lined HDPE Containers (capacity : 30 liter each).
  • Collect sifted PVPK-30 IP (1.250 kg) in Polybag (capacity: 2 kg).
  • Collect the sifted Talcum IP (1.400 kg), Cross Carmellose Sodium IP (1.750 kg), Crospovidone XL IP (2.500 kg), Aerosil IP (1.250 kg) in Polybag (capacity : 10 kg).
  • Collect the sifted Calcium Stearate IP (2.500 kg) in Polybag (capacity: 5 kg)

STEP – II (BINDER PREPARATION):

Take Isopropyl Alcohol (23.500 liter) in SS Container (capacity: 30 liter) and add PVPK-30 IP (1.250 kg) in it.  Mix together by Portable Stirrer continuously stirring till dissolved properly in IPA.

Mixing Time: 10 minutes (To be validated in next batch)

Filter  the solution with  filter cloth 100 # in SS Container (capacity: 30 liter).

STEP – III (DRY MIXING):

Transfer the sifted Pantoprazole Sodium IP, Mannitol IP, Cross Carmellose Sodium IP and Sodium Carbonate in Mass Mixer (capacity: 100 liter) and dry mix the materials till uniform mixing.

Mixing Time: 10 minutes.(To be validated in next batch)

Mixing Speed: 36 RPM

Paddle (Blades) Timing: 05 minutes in clockwise direction & 05 minutes in anti-clockwise direction.

STEP –IV (BINDING OF DRY MIX MATERIAL):

Slowly add the binder of Step-II in dry mix materials of Step-III and mix for 10 minutes till uniform binding and after binding, collect the wet mass into sixteen Trays (capacity: 3.000 kg each).

Mixing Time: 10 minutes

Mixing Speed: 36 RPM

Paddle (Blades) Timing: 05 minutes in clockwise direction & 05 minutes in anti-clockwise direction.

STEP –V (DRYING):

Dry the wet mass of Step -IV as follows:

Load these sixteen trays in Tray Dryer.

First air dry the granules for 30 minutes in Tray Dryer. Ensure that Heaters are in OFF mode during air drying. After 30 minutes of air drying, Switch ON the heaters and set the temperature at 35oC and dry the granules , until the LOD of granules is between 1.0 to 1.5% at 105oC checked by Halogen Moisture Balance.

Air Drying Time: 30 minutes (Heaters should be OFF)

Drying Time: 04 to 05 Hours. (To be validated in next batch)

Drying Temperature: 350C (After Air Drying)

Raking Frequency: After every 30 minutes.

STEP-VI (SIZING/MILLING):

Check Sieve Integrity (before sifting and after sifting).

Set the Vibro Sifter and fix the sieve 40 # and sieve the dried material of Step-V. Collect the sized material into two Poly-lined HDPE containers (capacity: 30 liter each).

 

STEP – VII (PRE –LUBRICATION):

Load the sized granules of Step-VI in Double Cone Blender (capacity : 200 liter) and add sifted Talcum IP , Cross Carmellose Sodium IP, Crospovidone XL IP and Aerosil IP, mix properly till uniform mixing of sized 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 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 (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

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:

  • Take Tare Weight of two Poly-lined HDPE Containers (capacity: 30 liter each), record the Tare Weight in BMR and unload the above blended material from Double Cone Blender in Poly-lined HDPE Containers (capacity: 30 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 Container.
  • Batch Yield of Lubricated granules:

Theoretical Batch Yield: 55.000 kg (100 %)

Actual Batch Yield Limit NLT 54.450 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:

   NOTE: Turn ON the sodium lamp and switch OFF all lights before starting the compression and use black polybags to store the tablets.

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.
  • After confirmation continue the compression with 35 stations (B-Tooling) Compression Machine. 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 —– —–
4.        Machine Speed 20 RPM -22 RPM —– —–
5.        Common Name of Die Peace
6.        Upper Punch Size 6.5  mm ­—– —–
7.        Lower Punch Size 6.5  mm —– —–
8.        Diameter of the tablet 6.5 mm 6/Individual 2 hours
9.        Thickness of Tablets 3.17 mm ± 0.2 mm 6/Individual 2 hours
10.    Weight of 20 Tablets 2.200 gm. ± 2 % 20/Composite 30 minutes
11.    Product Description Off white color, round shape, biconvex, uncoated tablet having both side plain 20/Composite 30 minutes
12.    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 % 20/Composite 01 hour
13.    Standard Average Weight of Tablets 110 mg ± 2 % 20/Individual 30 minutes
14.    Hardness NLT 3.0 kg/cm2 6/Individual 30 minutes
15.    Disintegration Time NMT 15 min 6/Composite 01 hour
16.    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 two Poly-lined HDPE Containers as given below in 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 two Poly-lined HDPE Containers (capacity: 30 liter each), record the Tare Weight in BMR and transfer the compressed tablets in Poly-lined HDPE Containers (capacity: 30 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: 55.000 kg (100 %)

Actual Batch Yield Limit NLT 54.450 kg (NLT 99 %) (To be established in next batch)

STEP – IV:

  • After completion of compression of tablets, clean the Compression Machine as per cleaning SOP.

NOTE: For this product the lot size of 500000 tablets is taken which is divided into different sub lots (batches of different quantities) as per the order of the customers.

In order to standardized the Coating Procedure we are taking the Batch Size of 100000 tablets for coating in this MFR.

6.3 COATING: FOR 100000 Tablets:

NOTE: Switch ON sodium lamp and Switch OFF all lights and use black polybags to store the tablets.

  • Verify the Net Weight of the received compressed tablets for coating as per status label and after confirmation continue for tablet coating.

STEP – I (COATING MATERIALS SEAL COAT DETAILS):      

Sr. No Material Name Batch Quantity
1. Instacoat  Solution Transparent IC-S-1643 0.110 kg
2. Isopropyl Alcohol IP 0.630 liter
3. Dichloromethane USP

 

1.470 liter

STEP – II (COATING MATERIALS ENTERIC COATING DETAILS):      

Sr. No Material Name Batch Quantity
1. Instacoat EN Solution White IC-EN-001 1.100 kg
2. Isopropyl Alcohol IP 6.270 liter
3. Dichloromethane USP

 

14.630 liter
4. Yellow oxide of iron 0.055 kg (To be validated according to the reference sample of product)

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-III (LIST OF EQUIPMENTS FOR COATING):

Sr. No. Machineries/Equipments Capacity Equipment ID.
1. Coating  Machine and Coating Pan 24″ SC/PD/COT/04
2. Spray Gun 01
3. Filter Cloth 100 # 0.5 Meter
4. Portable Stirrer
5. SS Containers 10 liter (02 No’s), 30 liter (02 No’s)
6. Poly-lined HDPE Containers with lid 30  liter (01 No.)

STEP – IV (PREPARATION OF SEAL COAT SOLUTION):

  • Take Isopropyl Alcohol IP (0.630 liter) and Dichloromethane USP (1.470 liter) in SS Container (capacity: 10 liter) and add Instacoat Solution Transparent IC-S-1643 (0.110 kg), mix together by Portable Stirrer properly continuously stirring till uniform mixing achieved.

Speed of stirrer: Constant.

Mixing Time: 15 minutes (To be validated in next batch)

  • Filter the seal coating solution with Filter Cloth 100 # in SS Container (capacity: 10 liter).
  • Keep the solution for 10 minutes and after 10 minutes start the Seal Coating process with Seal coating solution

STEP – V (COATING PROCEDURE FOR SEAL COAT OF TABLETS):

NOTE: Use sodium lamp and switch OFF lights and use black polybags to store the tablets.

  • Coating will be done in one lot, take total compressed tablets for coating (11.000 kg).
  • Load the tablets in coating pan (Capacity: 24″), start the hot air blower, set the inlet air temperature at 60°C to 65°C and start the exhaust fan & warm the tablets bed 30°C to 35°C.
  • After warming up the tablets, take weight of 100 warm tablets and also take weight of 100 tablets after Seal Coat and record the weight in BMR for calculation of weight buildup of tablets after Seal Coat.
  • Set the coating parameter as given in below table and start the coating process by starting coating spray through gun.
  • After completion of Seal Coating, calculate the weight gain by using below Formula in the table.
Parameter Specification
No. of Baffles in coating pan 03
No. of Guns 01
Inlet Temperature 60°C to 65°C (To be validated in next batch)
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 10 inch
BED Temperature 300C to 35 0C (To be validated in next batch)
Pan RPM 13 to 15 RPM
% Weight Gain

 (Up to 1 %)

Weight of tablets after  Seal Coat – Weight of uncoated warmed tablets   x 100

                         Weight of tablets after Seal Coat

Seal Coating Time 02 Hour (To be validated in next batch)

 

STEP – VI (PREPARATION OF ENTERIC COATING SOLUTION):

  • Take Isopropyl Alcohol IP (6.270 liter) and Dichloromethane USP (14.630 liter) in SS Container (capacity; 30 liter) and add Instacoat EN Solution White IC-EN-001(1.100 kg), mix together by Portable Stirrer properly continuously stirring till uniform mixing achieved.

Speed of stirrer: Constant.

Mixing Time: 15 minutes (To be validated in next batch)

  • After uniform mixing add color Yellow oxide of iron IP (0.055 kg) in the above solution and mix for 05 minutes with stirrer till uniform mixing achieved.
  • Filter the Enteric coating solution with Filter Cloth 100 # in one SS Container (capacity: 30 liter)
  • Keep the solution, after completion of Seal Coating, start the enteric coating process with enteric coating solution.

STEP – VII (COATING PROCEDURE FOR ENTERIC COATING OF TABLETS):

  • Set the coating parameter as given in below table and start the enteric coating process by starting coating spray through gun.
Parameter Specification
No. of Baffles in coating pan 03
No. of Guns 01
Inlet Temperature 60°C to 65°C (To be validated in next batch)
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 10 inch
BED Temperature 300C to 35 0C (To be validated in next batch)
Pan RPM 13 to 15 RPM
% Weight Gain

 (8 to 10 %)

Weight of Enteric Coated Tablets – Weight of Seal Coated Tablets   x 100

                         Weight of Enteric Coated Tablets

Enteric Coating Time  Coating Time: 06 Hours (To be validated in next batch)

 

 

  • After completion of Enteric coating, take weight of 100 Enteric coated tablet and record the weight in BMR and calculated the weight gain by using Weight Gain Formula given in above table of Step- VII

 

STEP – VII (COATING IN-PROCESS CHECK PARAMETERS):

  • After completion of Enteric Coating perform the In Process checks as per below parameters.
S.No. Parameters Standard No. of Tablets In-Process Frequency
1 Product Description Yellow color, round shape, biconvex, enteric coated tablet having both side plain 20 No.  

 

 

After batch completion

2 Weight of 20 Tablets after coating 2.420 gm.(8 % to 10 % weight gain) 20 No.
3 Average Weight after coating 121 mg .(8 % to 10 % 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 3.88 mm ± 0.2 mm 6 No.
6 Disintegration Time (Acid Medium) In 0.1M HCl – Should not crack in two hours 6 No.
7 Disintegration Time (In Phosphate Buffer) Should disintegrate within one hour in mixed phosphate buffer pH = 6.8
8  Dissolution in Acid Medium (Gastro Resistance) Pantoprazole Sodium (as Enteric Coated tablet)

Should be dissolved less than 15 %

 

20 No.
9  Dissolution in Phosphate Buffer Pantoprazole Sodium (as Enteric Coated tablet)

Should be dissolved more than 80 %

 

STEP – IX:

  • Send the composite sample of coated tablets (Qty.30 tablets) to QC department for analysis.

STEP – X:

  • Take Tare Weight of one Poly-lined HDPE Containers (capacity: 30 liter ), record the Tare Weight in BMR and transfer the coated tablets in Poly-lined HDPE Containers (capacity: 30 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: 12.100 kg (100 %)
  • Actual Batch Yield Limit NLT 11.979 kg (NLT 99 %) (To be established in next batch).

By iamraj