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.	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 35^oC in Tray Dryer and dry the granules until the LOD of granules is between 1.0 to 1.5% at 105^oC 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