Diclofenac Potassium 50 mg and Serratiopeptidase 10 mg Tablets and its Mechanism of action

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Diclofenac Potassium 50 mg and Serratiopeptidase 10 mg Tablets and its Mechanism of action

Description of Serratiopeptidase 10Mg + Diclofenac Potassium 50Mg Tablets is a combination of the two pharmacological classes Diclofenac Potassium and Serratiopeptidase, which is used to alleviate pain. Diclofenac Potassium is a non-steroidal anti-inflammatory medicine (NSAID) that acts by preventing the release of pain-causing chemical messengers in the brain (redness and swelling). Serratiopeptidase is an enzyme that aids healing by degrading aberrant proteins at the site of inflammation.

Diclofenac Potassium is a non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions.

Serratiopeptidase is a proteolytic enzyme (protease) produced by enterobacterium Serratia sp. E-15 used in the prevention of pain and swelling.

For the treatment of primary dysmenorrhea.

For the treatment of mild to moderate pain.

For the relief from the signs and symptoms of osteoarthritis.

For the relief from the signs and symptoms of rheumatoid arthritis.

Chronic inflammation.

Headaches, muscle, and joint pain.

Serious diseases like cancer and heart disease.

Superficial thrombophlebitis.

Postoperative & traumatic swelling.

Acute or chronic ear, nose, or throat disorder.

Uses

Diclofenac Potassium+Serratiopeptidase Tablet is a combination of medications intended to relieve pain, inflammation, and swelling in the short term. It prevents the release of chemical messengers in the brain that alerts us to the presence of pain. Back pain, toothache, periods of pain, earache, throat pain, and arthritis pain are all efficiently relieved by it.

Mechanism of action

Diclofenac inhibits cyclooxygenase-1 and -2, the enzymes responsible for the production of prostaglandin (PG) G2 which is the precursor to other PGs. These molecules have broad activity in pain and inflammation and the inhibition of their production is the common mechanism linking each effect of diclofenac.

PGE2 is the primary PG involved in the modulation of nociception. It mediates peripheral sensitization through a variety of effects. PGE2 activates the Gq-coupled EP1 receptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces the action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGE2 also activates the EP4 receptor, coupled to Gs, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member 1 (TRPV1) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the P2X3 purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGE2 acts via EP3 to increase sensitivity to bradykinin and via EP2 to further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EP2 receptor which couples to Gs. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low-intensity stimuli to generate pain signals. PGI2 is known to play a role via its Gs-coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain.

PGI2 and PGE2 contribute to acute inflammation via their IP and EP2 receptors. Similarly to β adrenergic receptors these are Gs-coupled and mediate vasodilation through the AC/PKA pathway. PGE2 also contributes by increasing leukocyte adhesion to the endothelium and attracting the cells to the site of injury.17 PGD2 plays a role in the activation of endothelial cell release of cytokines through its DP1 receptor.11 PGI2 and PGE2 modulate T-helper cell activation and differentiation through IP, EP2, and EP4 receptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation.

PGE2 can cross the blood-brain barrier and act on excitatory Gq EP3 receptors on thermoregulatory neurons in the hypothalamus.17 This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGE2 thereby reducing the activity of these neurons.

Precaution

Women who are pregnant or breastfeeding should seek medical advice before beginning treatment. You should also avoid consuming alcohol while taking this medication because it can cause sleepiness.

Direction

You can take Diclofenac Potassium +Serratiopeptidase Tablet with or without food. The dosage will be determined by the reason you’re taking it and how well it relieves your symptoms. You should follow your doctor’s instructions. Do not take more or use it for longer than the doctor has prescribed.

Side Effects

Nausea, diarrhea, vomiting, heartburn, stomach discomfort, indigestion, and loss of appetite are the most typical side effects of this medication. If any of these side effects annoy you or become worse, contact your doctor. Your doctor may be able to advise you on how to avoid or mitigate the negative effects.

Direction to Use | Diclofenac + Serratiopeptidase Tablet

Take diclofenac + serratiopeptidase tablet with food to avoid stomach upset.

Do not consume alcohol while taking diclofenac + serratiopeptidase tablet as it may cause liver damage.

Pregnant women and breasting mothers should not take this pain killer without consulting a doctor.

Also, this tablet of diclofenac + Serratiopeptidase may cause dizziness so avoid taking this medication of diclofenac + serratiopeptidase tablet.

Keep this tablet of diclofenac + serratiopeptidase tablet in a cool and dry place and avoid taking cough-related medicine without consulting a doctor.

TABLE OF CONTENTS FOR Diclofenac Potassium

S.NO. TITLE Page No.
1.0 PRODUCT DETAILS
2.0 MANUFACTURING FORMULA
3.0 LIST OF EQUIPMENT
4.0 GENERAL PRECAUTIONS
5.0 MANUFACTURING INSTRUCTIONS
6.0

 

 

 

 MANUFACTURING PROCESS DETAILS
6.1 GRANULATION
6.2 COMPRESSION
6.3  COATING
6.4 BRAND DETAILS

1.0 PRODUCT DETAILS FOR Diclofenac Potassium :

Product Name Diclofenac Potassium and Serratiopeptidase Tablets
Product Description Yellow color round shape, biconvex,  enteric-coated tablets having both side plain
Strength Diclofenac Potassium BP 50 mg and  Serratiopeptidase IP10 mg
Label claim

 

 Each enteric-coated tablet contains:

Diclofenac Potassium BP – 50 mg

Serratiopeptidase  IP – 10 mg
Batch Size 5,00,000 Tablets
Average Weight 112 mg (Uncoated tablets)

123.200 mg (Enteric-coated tablets)
Shelf Life 24 months
Storage Store in a cool, dry, and dark place below 250C
Drug Category Non-steroidal Anti- Inflammatory Drug

2.0 MANUFACTURING FORMULA FOR Diclofenac Potassium:

Material Name Grade Category Quantity per Unit

(In mg)

 Overages Batch Qty.

(In Kg)
Dry Mixing Part -I
 Diclofenac Potassium   BP API 50 mg —- 25.000 kg
MCCP-PH-102 IP Diluent 27.4 mg —- 13.700 kg
Binder For PART-I
PVPK-30 IP Binder 0.8 mg —- 0.400 kg
Isopropyl Alcohol IP Solvent 0.0426 ml —- 21.310 liter
Dry Mixing PART-II
Serratiopeptidase Plain IP API 10 mg 20 % 6.000 kg
MCCP-PH-102 IP Diluent 10 mg —- 5.000 kg
Binder For PART- II
PVPK-30 IP Binder 0.20 mg —- 0.100 kg
Isopropyl Alcohol (IPA) IP Solvent 0.0121 ml —- 6.050 liter
Lubricant
Talcum IP Anti-caking agent 2.5 mg —- 1.250 kg
Cross Carmellose Sodium IP Disintegrant 2.0 mg —- 1.000 kg
Talcum IP Anti-caking agent 2.5 mg —- 1.250 kg
Cross Carmellose Sodium IP Disintegrant 2.0 mg —- 1.000 kg
Crospovidone XL IP Disintegrant 2.2 mg —- 1.100 kg
Sodium Starch Glycolate IP Disintegrant 2.5 mg —- 1.250 kg
Aerosil IP Glidant 1.0 mg —- 0.500 kg
Magnesium Stearate IP Anti-adherent 1.4 mg —- 0.700 kg

3.0 LIST OF EQUIPMENT FOR Diclofenac Potassium:                         

  Sr. No. Machinery/Equipment Capacity Equipment ID.
1. Weighing Balance 100 kg
2.  Vibro Sifter (with SS Sieves No’s 14,20,30, 40 and 60) 30 inch dia
3. Mass Mixer with propeller 100 liter
4. Portable Stirrer — —
5. Tray Dryer 48 Trays
6. Multi-Mill (screen size 1.5 mm)
7. Double Cone Blender 200 liter
8. Halogen Moisture Balance —
9. Compression Machine 35 Station
10. SS Containers with lid 10 liter ,30 liter —
11. Poly-lined HDPE Containers with lid 30  liter,45 liter —
12. Filter Cloth 100 # 0.5 Meter
13. Polybags 1 kg,10 kg,20 kg,25 kg —

4.0 GENERAL PRECAUTIONS FOR Diclofenac Potassium:

  • API Description Diclofenac Potassium: A white or slightly yellowish, slightly hygroscopic crystalline powder.
  • API Description Serratiopeptidase (Plain): A greyish white to pale brown powder with a characteristic odor.
  • 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 products or a mixture of Active Ingredients and Excipients, wear gloves and a mask to avoid exposure and contact with any body parts.

5.0 MANUFACTURING INSTRUCTIONS FOR Diclofenac Potassium:

  • All activities shall be performed as per current SOPs.
  • Take the line clearance for all equipment from QA before starting the manufacturing operation during 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 a correct entry.

6.0 MANUFACTURING PROCESS DETAILS FOR Diclofenac Potassium:

6.1 GRANULATION FOR Diclofenac Potassium:

STEP – I (SIFTING) FOR Diclofenac Potassium :

  • 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 (Part-I)
Diclofenac Potassium BP 25.000 kg 40 #
MCCP PH-102 IP 13.700 kg 40 #
Binder for Part-I
PVPK-30 0.400 kg 20 #
Isopropyl Alcohol IP (IPA) 21.310 liter NA
Dry Mixing (Part-II)
Serratiopeptidase  Plain IP 6.000 kg 40 #
MCCP-PH-102 IP 5.000 kg 40 #
Binder for Part-II
PVPK-30 IP 0.100 kg 20 #
Isopropyl Alcohol IP (IPA) 6.050 liter NA
Lubricant
Talcum IP 1.250 kg 60 #
Cross Carmellose Sodium IP 1.000 kg 60 #
Crospovidone XL IP 1.100 kg 60 #
Sodium Starch Glycolate IP 1.250 kg 60#
Aerosil IP 0.500 kg 14 #
Magnesium Stearate 0.700 kg 60 #

NOT

  • Collect sifted Diclofenac Potassium IP (25.000 kg) and MCCP PH-102 IP (13.700 kg) into two Poly-Bags (capacity: 25 kg each).
  • Collect sifted PVPK-30 IP (0.400 kg) in one Polybag (capacity: 1 kg) for Part-I.
  • Collect sifted Serratiopeptidase IP (6.000 kg) and MCCP-PH-102 IP (5.000) into one Poly-Bag (capacity: 20 kg).
  • Collect sifted PVPK-30 IP (0.100 kg) in one Polybag (capacity: 1 kg) for Part-II.
  • Collect the sifted Talcum IP (1.250 kg), Cross Carmillose Sodium IP (1.000 kg), Crospovidone XL IP (1.100 kg), Sodium Starch Glycolate IP (1.250 kg) and Aerosil IP (0.500 kg) into one Poly-Bag (capacity : 10 kg).
  • Collect the sifted Magnesium Stearate IP (0.700 kg) into one Poly-Bag (capacity: 1 kg).

STEP – II (BINDER PREPARATION): PART-I:

  • Take Isopropyl Alcohol IP (21.310 liter) in SS Container (capacity: 30 liter) and add PVPK-30 IP (0.400 kg) in it. Mix together by Portable Stirrer continuously stirring till PVPK-30 IP dissolved properly in IPA.
  • Mixing Time: 10 minutes (To be validated in the next batch).
  • Filter it with 100# filter cloth in SS Container (capacity: 30 liters).

STEP – III (DRY MIXING): FOR PART-I:

  • Transfer the sifted Diclofenac Potassium BP and MCCP PH-102 IP in Mass Mixer (capacity: 100 liters) and dry mix the materials till uniform mixing.
  • Mixing Time: 10 minutes
  • Mixing Speed: 36 RPM.
  • Paddle (Blades) Timing: 05 minutes in a clockwise direction and 05 minutes in the anti-clockwise direction.

STEP –IV (BINDING OF DRY MIX MATERIAL): FOR PART-I:

  • 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 thirteen Trays (capacity: 3.000 kg each).
  • Mixing Time: 10 minutes
  • Mixing Speed: 36 RPM.
  • Paddle (Blades) Timing & Direction = 5 minutes in clockwise direction & 5 minutes in anti-clockwise direction 

STEP –V (DRYING):  FOR PART-I:

  • Dry the wet mass of Step -IV as follows:
  • Load these thirteen Trays of PART-I in the Tray Dryer.
  • First air dries the granules for 30 minutes in a Tray Dryer. Ensure that heaters are in OFF mode. After 30 minutes of air-drying, Switch ON the heaters and set the temperature at 35°C, and dry the granules, until the LOD of granules is achieved between 1.0 to 1.5 % at 105°C checking by Halogen Moisture Balance.
  • Air Drying Time: 30 minutes (Heaters should be OFF).
  • Drying Time: 03 Hours. (To be validated in the next batch).
  • Drying Temperature: 350C (After Air Drying).
  • Raking Frequency: After every 30 minutes.

STEP-VI (SIZING/MILLING): FOR PART-I:

  • Check Screen Integrity (before sifting and after sifting).
  • Mill the dried material of Step –V and pass through Multi Mill using screen size 1.5 mm and  collect milled material into one Poly-lined HDPE Containers (capacity:45 liters)
  • Blade Type: Both (Knife blades/Scraping blades)
  • Rotor Speed: 2000 RPM

STEP – VII (BINDER PREPARATION): FOR PART-II:

  • Take Isopropyl Alcohol IP (6.050 liters) in SS Container (capacity: 10 liters) and add PVPK-30 IP (0.100 kg) in it. Mix together by Portable Stirrer continuously stirring till PVPK-30 IP dissolved properly in IPA.
  • Mixing Time: 10 minutes (To be validated in next batch)
  • Filter it with 100# filter cloth in SS Container (capacity: 10 liters).

STEP – VIII (DRY MIXING): FOR PART-II:

  • Transfer the sifted Serratiopeptidase IP and MCCP PH-102 IP in SS Container (capacity: 30 liters) and dry mix the materials manually till uniform mixing.
  • Mixing Time: 10 minutes (manually) (To be validated in the next batch).

STEP –IX (BINDING OF DRY MIX MATERIAL): FOR PART-II:

  • Slowly add the binder PART-II of Step-VII in dry mix materials of Step-VIII and mix manually for 15 minutes till uniform binding and after binding, collect the wet mass into four Trays (capacity: 3.000 kg each).
  • Mixing Time: 15 minutes (manually) (To be validated in next batch)

STEP –X (DRYING): FOR PART-II:

  • Dry the wet mass of Step -IX as follows:
  • Load these four Trays of PART-II in the Tray Dryer.
  • First air dries the granules for 30 minutes in a Tray Dryer. Ensure that heaters are in OFF mode. After 30 minutes of air-drying Switch ON the heaters and set the temperature at 35°C and dry the granules, until the LOD of granules is achieved between 1.0 to 1.5 % at 105°C checking by Halogen Moisture Balance.
  • Air Drying Time: 30 minutes (To be validated in next batch)
  • Drying Time: 03 Hours. (To be validated in the next batch).
  • Drying Temperature: 350C (After Air Drying).
  • Raking Frequency: After every 30 minutes.
  • Rotor Speed: 2000 RPM 

STEP-XI (SIZING/MILLING): FOR PART-II:

  • Check Sieve Integrity (before sifting and after sifting).
  • Set the Vibro Sifter and fix the sieve 30 # and sieve the dried material of Step-X. Collect the sized material in one Poly-lined HDPE Container (capacity: 30 liters).

STEP – XII (PRE –LUBRICATION):

  • Load the milled granules of Step-VI (PART-I) and sized granules of Step-XI (PART-II) in Double Cone Blender (capacity: 200 liters) and add sifted Talcum IP, Cross Carmellose Sodium IP, Crospovidone XL IP, Sodium Starch Glycolate IP, and Aerosil IP, mix properly till uniform mixing of milled and 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 – XIII (LUBRICATION):

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

STEP- XIV (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 of Diclofenac Potassium

Blend Uniformity of Serratiopeptidase

Blend Assay

LOD

Bulk Density

Tapped Density

Compressibility Index

Hausner Ratio

 Yellow free flowing granular powder

90 % to 110 %

NLT 95 %

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 – XV:

  • Take Tare Weight of two Poly-lined HDPE Containers (capacity: 30 liters each), record the Tare Weight in BMR and unload the above-blended material from Double Cone Blender in Poly-lined HDPE Containers (capacity: 30 liters 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: 56.000 kg (100 %)

Actual Batch Yield Limit: 55.440 kg (NLT 99 %) (To be established in next batch).

STEP – XVI:

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

6.2 COMPRESSION:

STEP – I:                                

  • After receiving QC approval for the blend, verify the Net Weight of the received blend as per the 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 conditions. 
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 18 RPM -20 RPM —– —–
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 2.90 mm ± 0.2 mm 6/Individual 2 hours
10.    Weight of 20 Tablets 2.240 gm. ± 2 % 20/Composite 30 minutes
11.    Product Description Yellow color round shape, biconvex, uncoated tablets 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 % —– 01 hour
13.    Standard Average Weight of Tablets 112 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 liters 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 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 liters each), record the Tare Weight in BMR and transfer the compressed tablets in Poly-lined HDPE Containers (capacity: 30 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 Containers.
  • Batch Yield of Compressed Tablets:
  • Theoretical Batch Yield: 56.000 kg (100 %).
  • Actual Batch Yield Limit: 55.440 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 standardize the Coating Procedure, we are taking the Batch Size of 100000 tablets for coating in this MFR.

6.3 COATING: (FOR 1, 00,000 Tablets)

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

 STEP – I (COATING MATERIALS FOR SEAL COATING DETAILS):      

Sr. No Material Name Batch Quantity
1. Instacoat  Solution Transparent IC-S-1643 0.112 kg
2. Isopropyl Alcohol IP 0.640 liter
3. Dichloromethane USP

 

 1.490 liter

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

Sr. No Material Name Batch Quantity
1. Instacoat EN Solution White IC-EN-001 1.120 kg
2. Isopropyl Alcohol IP 6.384 liter
3. Dichloromethane USP

 

 14.896 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 EQUIPMENT FOR COATING):

Sr. No. Machinery/Equipment 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 (02No’s) —
6. Poly-lined HDPE Containers with lid 30  liter (01 No.) —

STEP – IV (PREPARATION OF SEAL COATING SOLUTION):

  • Take Isopropyl Alcohol IP (0.640 liter) and Dichloromethane USP (1.490 liter) in SS Container (capacity: 10 liter) and add Instacoat Solution Transparent IC-S-1643 (0.112 kg). Mix together by Portable Stirrer properly continuously stirring till uniform mixing is 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 liters) and proceed for Seal coating with the seal coating solution.

STEP – V (COATING PROCEDURE FOR SEAL COATING):

  • The coating will be done in one lot for 1,00,000 tablets, take total compressed tablets for coating (11.200 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 the weight of 100 warm 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 of tablets.
  • Set the coating parameter as given in the below table and start the coating process by starting coating spray from the gun.
  • After completion of Seal Coating, calculate the weight gain by using the below Formula in the table.
Parameter Specification
No. of Baffles in a 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 Coating – Weight of uncoated warmed tablets   x 100 / Weight of tablets after Seal Coating
Seal Coating Time 01 Hour (To be validated in next batch)

STEP – VI (PREPARATION OF ENTERIC COATING SOLUTION):

  • Take Isopropyl Alcohol IP (6.384 liters) and Dichloromethane USP (14.896 liters) in SS Container (capacity; 30 liters) and add Instacoat EN Solution White IC-EN-001(1.120 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 is achieved.
  • Filter the Enteric coating solution with  Filter Cloth 100 # in one SS Container (capacity: 30 liters)
  • Keep the solution, after completion of Seal Coating, start the enteric coating process with the enteric coating solution.

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

  • Set the coating parameter as given in the below table and start the enteric coating process by starting coating spray through the gun.
Parameter Specification
No. of Baffles in the 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

 ( 08 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 100 Enteric-coated tablets and record the weight in BMR, and calculate the weight gain by using the above Weight Gain Formula.

Diclofenac Potassium

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

  • After completion of Enteric Coating, perform the In Process checks as per the 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 2.464 gm.(8 % to 10 % weight gain) 20 No.
3 Average Weight after coating 123.200 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 —

STEP – IX:

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

STEP – X:

  • Take Tare Weight of one Poly-lined HDPE Containers (capacity: 30 liters), record the Tare Weight in BMR and transfer the coated tablets in Poly-lined HDPE Containers (capacity: 30 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: 12.320 kg (100 %)

Actual Batch Yield Limit NLT 12.197 kg (NLT 99 %) (To be established in next batch).

References: Drug Bank Online

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