MFR of Trypsin 48 mg, Bromelain 90 mg and Rutoside Trihydrate 100 mg Tablets

MFR of Trypsin 48 mg, Bromelain 90 mg and Rutoside Trihydrate 100 mg Tablets

TABLE OF CONTENTS

 

S.NO.TITLEPage No.
1.0PRODUCT DETAILS02 of 09
2.0MANUFACTURING FORMULA02 of 09
3.0LIST OF EQUIPMENTS02 of 09

 

4.0GENERAL PRECAUTIONS03 of 09
5.0MANUFACTURING INSTRUCTIONS03 of 09
6.0

 

 

 

MANUFACTURING PROCESS DETAILS
6.1GRANULATION03 of 09
6.2COMPRESSION05 of 09
6.3COATING06 of 09
6.4BRAND DETAILS09 of 09

 

1.0 PRODUCT DETAILS:

Product NameTrypsin, Bromelain and Rutoside Trihydrate Tablets
Product DescriptionPink color, round shape, biconvex, enteric-coated tablets having both side plain
StrengthTrypsin BP                          48 mg

Bromelain                           90 mg

Rutoside Trihydrate  BP    100 mg

Label claim

 

Each enteric-coated tablet contains:

Trypsin BP                          48 mg

Bromelain                           90 mg

Rutoside Trihydrate  BP    100 mg

Batch Size2,00,000 Tablets
Average Weight500 mg (Uncoated tablets)

550 mg (Enteric coated tablets)

Shelf Life24 months
StorageStore in a cool, dry and dark place below 25 0C
Drug CategoryAnalgesic, Anti-Inflammatory Drug

2.0 MANUFACTURING FORMULA:

Material NameGradeCategoryQuantity per Unit (In mg)OveragesBatch Qty.

(In kg)

Dry Mixing – I
TrypsinBPAPI48 mg25 %12.000 kg
BromelainNAAPI90 mg20 %21.600 kg
Rutoside TrihydrateBPAPI100 mg12 %22.400 kg
MCCP PH-112IPDiluent40 mg8.000 kg
MCCP PH -102IPDiluent143.50 mg28.700 kg
Lubricant
TalcumIPAnti caking agent10 mg2.000 kg
Sodium Starch GlycolateIPDisintegrant7.5 mg1.500 kg
Crospovidone XLIPDisintegrant7.5 mg1.500 kg
Cross Carmellose SodiumIPDisintegrant7.5 mg1.500 kg
Magnesium StearateIPAnti -adherent4 mg0.800 kg

3.0 LIST OF EQUIPMENTS:                         

 Sr. No.Machineries/EquipmentsCapacityEquipment ID.
1.Weighing Balance100 kgSC/PD/WBL/03
2.Vibro Sifter

(with SS Sieves No’s 24, 40, and 60 )

30 inch diaSC/PD/SFT/01

SC/PD/SFT/02

3.Double Cone Blender400 literSC/PD/GR/O3
4.Halogen Moisture BalanceSC/QC/007
5.Compression Machine27 StationSC/PD/CPM/03,SC/PD/CPM/05
6.Poly-lined HDPE Containers with lid45 liter (09 Noes)
7.Polybags01 kg (01 No.),

10 kg (01 No.)

GENERAL PRECAUTIONS:

  • API Description Trypsin: A white or almost white crystalline powder.
  • API Description Bromelain: Off white to the pale brown color powder.
  • API Description Rutoside Trihydrate: Yellow or greenish-yellow color crystalline powder.
  • All the Manufacturing Activities shall be performed under controlled conditions (temperature NMT 250C and relative humidity NMT 40%).
  • 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.

MANUFACTURING INSTRUCTIONS:

  • All activities shall be performed as per current SOPs.
  • Take the line clearance for every machine from QA before starting the manufacturing operation from batch to batch and product to product change over.
  • Do not overwrite the entry. In case of mistake, cancel the entry by a single line with sign & date and make the correct entry.

6.0 MANUFACTURING PROCESS DETAILS:

  6.1 GRANULATION:

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-I
Trypsin BP12.000 kg24 #
Bromelain21.600 kg24 #
Rutoside Trihydrate   BP22.400 kg24 #
MCCP PH -112 IP8.000 kg40 #
MCCP PH -102 IP28.700 kg40 #
Lubricants
Talcum IP2.000 kg60 #
Sodium Starch Glycolate IP1.500 kg60 #
Crospovidone XL IP1.500 kg60 #
Cross Carmellose Sodium IP1.500 kg60 #
Magnesium Stearate0.800 kg60 #

 

  • Collect sifted Trypsin BP (12.000 kg), Bromelain (21.600 kg), Rutoside Trihydrate BP (22.400 kg), MCCP PH-112 IP (8.000 kg) and MCCP PH-102 IP (28.700 kg) in three Poly-lined HDPE Containers (capacity: 45 liter each).
  • Collect sifted Talcum IP (2.000 kg), Sodium Starch Glycolate IP (1.500 kg), Crospovidone XL IP (1.500 kg) and Cross Carmellose Sodium IP (1.500 kg) in one Polybag (capacity: 10 kg).
  • Collect the sifted Magnesium Stearate IP (0.800 kg) in one Polybag (capacity: 1 kg).

STEP – II (DRY MIXING):

  • Transfer the sifted Trypsin BP, Bromelain, Rutoside Trihydrate BP, MCCP PH-112 IP, and MCCP PH-102 IP in Double Cone Blender (capacity: 400 liters) and dry mix the materials till uniform mixing.
  • Mixing Time: 20 minutes (10 minutes clockwise and 10 minutes anticlockwise direction).
  • (To be validated in next batch)
  • Mixing Speed: 10 RPM.

STEP – III (PRE –LUBRICATION):

  • Add the sifted Talcum IP, Sodium Starch Glycolate IP, Crospovidone XL IP, and Cross Carmellose Sodium in Double Cone Blender with Step-II and mix properly till uniform mixing of sifted materials with Trypsin BP, Bromelain, Rutoside Trihydrate BP, and Pre-Lubricating Materials.
  • Mixing Time: 30 minutes (15 minutes clockwise direction and 15 minutes anti-clockwise direction
  • Mixing Speed: 10 RPM.

STEP – IV (LUBRICATION):

  • Add the sifted Magnesium Stearate IP in Double Cone Blender with Step-III of Pre-Lubricated Material and mix properly till uniform mixing of materials with Magnesium Stearate IP.
  • Mixing Time: 05 minutes (clockwise direction)
  • Mixing Speed: 10 RPM.

STEP- V (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:
TestSpecification
Appearance of blend

Blend Uniformity

Blend Assay

LOD

Bulk Density

Tapped Density

Compressibility Index

Hausner Ratio

Yellow color free flowing granular powder

90 % to 110 %

98 % to 103 %

To be established in next batch

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 – VI:

  • Take Tare Weight of three Poly-lined HDPE Containers (capacity: 45 liter each), record the Tare Weight in BMR and unload the above blended material from Double Cone Blender in Poly-lined HDPE Containers (capacity: 45 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 the following details – Product Name, Batch No., Batch Size, Mfg. Date, Exp. Date, Tare Weight, Gross Weight, and Net Weight on the Poly-lined HDPE Containers.
  • Batch Yield of Lubricated granules:
  • Theoretical Batch Yield: 100.000 kg (100 %).
  • Actual Batch Yield Limit NLT 99 .000 kg (NLT 99 %) (To be established in next batch).

STEP – VII:

  • Clean all equipments used in the granulation as per respective equipment cleaning SOP.

COMPRESSION:

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 of the result continues the compression 27 stations (D-Tooling) Compression Machine. Compress the blend as per the following parameters and In Process checks under controlled environmental conditions.
S.NoParametersStandardNo. of Tablets In-Process   Frequency
1.       Feed frame alignment and adjustmentShould be satisfactory—–—–
2.       Lower Weight AssemblyShould be satisfactory—–—–
3.       Hydraulic Pressure5 -7 Tones—–—–
4.       Machine Speed12 RPM to 15 RPM—–—–
5.       Common Name of DieBig Para Coated
6.       Upper Punch Size12.5 mm­—–—–
7.       Lower Punch Size12.5 mm—–—–
8.       Die12.5 mm6/Individual2 hours
9.       Diameter of the tablet12.5 mm6/Individual2 hours
10.   Thickness of Tablets4.95 mm ±0.2 mm6/Individual2 hours
11.   Weight of 20 Tablets10.000 gm. ± 2%20/Composite30 minutes
12.   Product DescriptionYellow color, round shape, biconvex, uncoated tablets having both sides plain20/Composite30 minutes
13.   Uniformity of WeightNMT 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/Composite01 hour
14.   Standard Average Weight of Tablets500  mg ± 2 %20/Individual30 minutes
15.   HardnessNLT 4 kg/cm26/Individual30 minutes
16.   Disintegration TimeNMT 15 min6/Composite01 hour
17.   FriabilityNMT 1%20/Composite01 hour
  • Collect the compressed tablets in SS Containers (capacity: 20 liters each on both sides), when SS containers are filled with tablets, transfer the tablets in three 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 three Poly-lined HDPE Containers (capacity: 45 liters each), record the Tare Weight in BMR and transfer the compressed tablets in Poly-lined HDPE Containers (capacity: 45 liters 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 the 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: 100.00 kg (100 %).
  • Actual Batch Yield Limit NLT 99.000 kg (NLT 99 %) (To be established in next batch).

STEP – IV:

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

NOTE: For this product, the lot size of 200000 tablets is taken which is divided into different sub lots (batches of different quantities) as per the order of the customers.

In order to standardize the Coating Procedure, we are taking the Batch Size of 50000 tablets for coating in this MFR.

6.3 COATING: (FOR 50,000 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 DETAILS FOR SEAL COATING):

Sr. NoMaterial NameBatch Quantity
1.Instacoat Moistshield White (IC-MS 2398)0.250 kg.
2.Isopropyl Alcohol IP1.425 liter
3.Dichloromethane USP3.325 liter

STEP – II (COATING MATERIALS DETAILS FOR ENTERIC COATING):

Sr. NoMaterial NameBatch Quantity
1.Instacoat EN Solution White (IC-EN-001)2.500 kg
2.Isopropyl Alcohol IP14.250 liter
3.Dichloromethane USP33.250 liter
4.Ponceau 4R0.125 kg (To be validated according to the reference sample of products)

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 EQUIPMENT FOR COATING):

Sr. No.Machineries/EquipmentsCapacityEquipment ID.
1.Coating Machine and Coating Pan36″SC/PD/COT/02,
2.Spray Gun01
3.Filter Cloth 100 #0.5 meter
4.Portable Stirrer
5.SS Containers15 liter (02 No’s),65 liters (02 Noes)
6.Poly-lined HDPE containers with lid45 liter (01 No.)

STEP – IV (PREPARATION OF SEAL COATING SOLUTION):

  • Take Isopropyl Alcohol IP (1.425 liters) and Dichloromethane USP (3.325 liters) in SS Container (capacity: 15 liters) and add Instacoat Moistshield White IC-MS 2398 (0.250 kg). Mix together by Portable Stirrer properly continuously stirring till uniform mixing is achieved.

Speed of Stirrer: Constant.

Mixing Time: 20 minutes (To be validated in the next batch).

  • Filter the coating solution with Filter Cloth 100 # in SS Container (capacity: 15 liters).
  • 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 COATING OF TABLETS):

  • The coating will be done in one lot for 50,000 tablets, take total compressed tablets for coating (25.000 kg).
  • Load the tablets in coating pan (capacity: 36″), 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 the weight of 100 warmed tablets and also take the weight of 100 tablets after Seal coating and record the weight in BMR for calculation of weight buildup of tablets after Seal Coating.
  • Set the coating parameter as given in the below table and start the coating process by starting coating spray through the gun.
  • After completion of Seal Coating, calculate the weight gain by using the below Formula in the table.
ParameterSpecification
No. of Baffles in coating pan03
No. of Guns01
Inlet Temperature60°C to 65°C(To be validated in next batch)
Peristaltic Pump Speed2 to 4 RPM (To be validated in next batch)
Atomization2.5 to 3.0 kg/cm2
Gun to Tablet Bed Distance8 inch
BED Temperature300C to 35 0C (To be validated in next batch)
Pan RPM13 to 15 RPM
% Weight Gain

(Up to 1%)

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

                         Weight of tablets after Seal Coating

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

 

STEP – VI (PREPARATION OF ENTERIC COATING SOLUTION):

  • Take Isopropyl Alcohol IP (14.250 liters) and Dichloromethane USP (33.250 liters) in SS Container (capacity: 65 liters) and add Instacoat EN Solution White (IC-EN-001) (2.500 kg) and add color Ponceau 4R (0.125 kg) in it. Mix together by Portable Stirrer properly continuously stirring till uniform mixing is achieved.
  • Speed of stirrer: Constant.
  • Mixing Time: 20 minutes (To be validated in next batch)
  • Filter the coating solution with Filter Cloth 100# in SS Container (65 liters).
  • Keeps the solution, after completion of Seal Coating, proceed for Enteric coating process with Enteric coating solution.

  STEP – VII (ENTERIC COATING PROCEDURE OF TABLETS):

  • Set the coating parameter as given in the below table and start the enteric coating process by starting coating spray through the gun.
ParameterSpecification
No. of Baffles in a coating pan03
No. of Guns01
Inlet Temperature60°C to 65°C (To be validated in next batch)
Peristaltic Pump Speed2 to 4 RPM (To be validated in next batch)
Atomization2.5 to 3.0 kg/cm2
Gun to Tablet Bed Distance8 inch
BED Temperature300C to 35 0C (To be validated in next batch)
Pan RPM13 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 the weight of 10 Enteric coated tablets and record the weight in BMR, and calculated the weight gain by using the Weight Gain Formula given in the above table of Step-VII.

 

STEP – VIII (ENTERIC COATING IN-PROCESS CHECK PARAMETERS):

  • After completion of Enteric Coating perform the In Process checks as per the below parameters.
S.No.ParametersStandardNo. of TabletsIn-Process Frequency
1Product DescriptionPink color, round shape, biconvex, enteric coated tablet having both side plain20 No. 

 

 

 

 

After batch completion

2Weight of 20 Tablets after coating11.000 gm (8 % to 10 % weight gain)20 No.
3Average Weight after coating550 mg (8 % to 10 % weight gain)20 No.
4Individual 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.
5Thickness5.29 mm ± 0.2 mm6 No.
6Disintegration Time (Acid Medium)In 0.1M HCl – Should not crack in two hours6 No.
7Disintegration Time (In Phosphate Buffer)Should disintegrate within one hour in mixed phosphate buffer pH = 6.8

 STEP – IX:

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

STEP – X:

  • Take Tare Weight of one Poly-lined HDPE Containers (capacity: 45 liters), record the Tare Weight in BMR and transfer the coated tablets in Poly-lined HDPE Containers (capacity: 45 liters 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 the 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: 27.500 kg (100 %)
  • Actual Batch Yield Limit NLT 27.225 kg (NLT 99 %) (To be established in next batch).

 

 

 

Uncategorized