Formula Master: Aceclofenac 100 mg, Paracetamol 325 mg and Trypsin Chymotrypsin Tablets

Master Manufacturing Formula (MFR): Aceclofenac 100 mg, Paracetamol 325 mg and Trypsin-Chymotrypsin Tablets

Source: drugsformulations.com via archive.org

TABLE OF CONTENTS

1. Product Details
2. Manufacturing Formula
3. General Precautions
4. Manufacturing Instructions
5. Manufacturing Process Details
   1. Granulation
   2. Compression
   3. Coating

1.0 PRODUCT DETAILS

2.0 MANUFACTURING FORMULA

3.0 LIST OF EQUIPMENTS

4.0 GENERAL PRECAUTIONS

• Aceclofenac: A white or almost white crystalline powder.
• Paracetamol: A white crystals or a white crystalline powder.
• Trypsin-Chymotrypsin: A white or a white crystalline powder.
• All the Manufacturing Activities shall be performed under controlled conditions (temperature NMT 25° C 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.

5.0 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 during batch to batch and product to product change over.
• Do not overwrite the 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

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:

After sifting, divide sifted Aceclofenac IP (30.000 kg) in two equal parts for LOT-I and LOT-II (15.000 kg each) and collect in four Poly-lined HDPE Containers (capacity: 45 liter each).

After sifting, divide sifted Paracetamol IP (97.500 kg) in two equal parts for LOT-I and LOT-II (48.750 kg each) and collect in above Poly-lined HDPE Containers with Aceclofenac.

After sifting, divide sifted Starch (15.000 kg) in two equal parts for LOT-I and LOT-II (7.500 kg each) and collect in above Poly-lined HDPE Containers with Aceclofenac and Paracetamol.

After sifting, divide sifted MCCP Plain IP (11.034 kg) in two equal parts for LOT-I and LOT-II (5.517 kg each) and collect in above Poly-lined HDPE Containers.

Collect sifted Trypsin & Chymotrypsin (6.720 kg) in one Polybag (capacity: 10 kg).

Collect sifted PVPK-30 IP (0.900 kg) in Polybag (capacity: 1 kg).

Collect sifted Sodium Benzoate IP (0.348 kg) in one Polybag (capacity: 1 kg).

Collect sifted Starch IP (4.875 kg) in one Polybag (capacity: 5 kg).

Collect sifted Talcum IP (3.000 kg), MCCP-PH-102 IP (5.023 kg) and Sodium Starch Glycolate IP (2.400 kg) in one Polybag (capacity: 20 kg).

Collect sifted Magnesium Stearate IP (1.800 kg) in one Polybag (capacity: 2 kg).

STEP – II (BINDER PREPARATION-I): FOR LOT-I:

(a) Take purified water (50.00 liter) in Paste Kettle (capacity: 100 liter), heat the purified water to 35° C.

(b) Take purified water (5.00 liter, at temperature 35° C) from Paste Kettle of Step-II (a) in SS Container (capacity: 10 liter) and add sifted Sodium Benzoate IP (0.348 kg) and PVPK-30 IP (0.900 kg) and mix one by one with Stirrer till dissolved properly in water and make a solution.

(c) Heat the remaining purified water (45.000 liter) up to 80° C of Step-II (a) in Paste Kettle and add Gelatin (0.900 kg) and mix properly with continuously stirring till the Gelatin properly dissolved in heated water.

(d) Take purified water separately (10.000 liter, at room temperature) in SS Container (capacity: 20 liter) and slowly add Starch (4.875 kg) continuously stirring till uniform solution is ready.

(e) Add above solution of Step-II (d) to heated purified water of Step-II (c) in Paste Kettle with continuously stirring till uniform paste is ready.

(f) Add Step-II (b) solution with continuously stirring into Step-II (c) till final paste is ready.

(g) Transfer the ready paste by tilting the Paste Kettle in one SS Container (capacity: 100 liter). Cool the paste up to 35° C to 40° C.

(h) Divide paste (Qty. 67.123 kg) into two equal parts (Qty. 33.561 kg) for LOT-I and LOT-II in SS Containers (capacity: 70 liter each).

STEP – III (DRY MIXING): FOR LOT – I:

Transfer the sifted Aceclofenac IP, Paracetamol IP, Starch IP and MCCP Plain in Rapid Mixer Granulator (capacity: 160 liter) running at slow speed impeller (0.820 ampere) and dry mix the materials till uniform mixing.

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

Slowly add the binder LOT-I of Step – II (h) (33.561 kg) in dry mix materials of Step – III in Rapid Mixer Granulator running at slow speed impeller (1.02 ampere) for 5 minutes till binder addition. After binder addition run impeller and chopper both at slow speed (0.63 ampere) for 08 min and finally run both chopper and impeller on fast speed (0.97 ampere) for 02 minutes till uniform mixing. Unload the material in SS Container (capacity: 100 liter) from RMG by opening the discharge point with running impeller.

STEP – V (WET SCREENING): FOR LOT – I:

Check Screen Integrity (before screening and after screening). Take wet material from SS Container and pass through Multi-Mill with screen size 8 mm and collect the wet material in SS Container (capacity: 100 liter) and after screening transfer the wet material in a FBD bowl.

STEP – VI (DRYING-I): FOR LOT-I:

Dry the wet material of Step-V in FBD (capacity: 120 kg) until the LOD of granules is achieved between 2.5 to 3.0% at 105°C checking by Halogen Moisture Balance and after drying unload the material in two Poly-lined HDPE Containers (capacity: 45 liter each).

STEP – VII (SIZING/MILLING-I): FOR LOT – I:

Check Screen Integrity (before screening and after screening). Set the Vibro Sifter and fix the Sieve 18# and sieve the dried material of Step-VI and collect in two Poly-lined HDPE Containers (capacity: 45 liter each) and remaining retention after sieving, pass through the Multi-Mill using screen size 2 mm. After screening keep the screened material with sized material in above Poly-lined HDPE Containers. Weigh and record the sized/milled granules quantity.

FOR LOT – II: Please follow the same procedure of LOT – I of dry mixing, binding of dry mix material, wet screening, drying and sizing/milling.

STEP – VIII (PREPARATION OF ENTERIC COATED GRANULES OF TRYPSIN & CHYMOTRYPSIN):

(a) Binder Preparation for Enteric Coating: Take Isopropyl Alcohol IP (2.500 liter) and Dichloromethane USP (2.500 liter) in SS Container (capacity: 10 liter) and add Cellulose Acetate Phthalate IP (0.500 kg). Mix together by Portable Stirrer continuously stirring till dissolved properly. Mixing Time: 30 minutes (To be validated in next batch). Filter the solution with 100# filter cloth in SS Container (capacity: 10 liter).

(b) Enteric Coating of Trypsin & Chymotrypsin: Transfer the sifted Trypsin & Chymotrypsin in SS Container (capacity: 20 liter) and slowly add the enteric coating solution and coat the API manually with enteric coating solution till uniform coating. Mixing Time: 05 minutes (manually) (To be validated in next batch).

(c) Wet Sizing: Pass through sieve size 10# manually and collect in three Trays (capacity: 3.000 kg each).

(d) Drying: Load three Trays in Tray Dryer. Air dry for 30 minutes (heaters OFF). Then set temperature at 35°C and dry until LOD between 1.0 to 1.5% at 105°C.

(e) Sizing/Milling: Set the Vibro Sifter and fix the sieve 18# and sieve the dried granules. Collect the sieved material in Polybag (capacity: 10 kg).

STEP – IX (PRE-LUBRICATION):

Load the sized/milled granules of Step-VII of LOT-I and LOT-II and sized granules of Step-VIII (e) in Octagonal Blender (capacity: 500 liter) and add sifted Talcum IP, MCCP-PH-102 and Sodium Starch Glycolate, mix properly till uniform mixing.

STEP – X (LUBRICATION):

Add the sifted Magnesium Stearate IP and mix properly till uniform mixing.

STEP – XI (BLEND SAMPLE ANALYSIS):

After completion of lubrication, collect composite blend sample (Qty. 10 gm) and send to QC for analysis:

STEP – XII:

Take Tare Weight of five Poly-lined HDPE Containers (capacity: 45 liter each), record the Tare Weight in BMR and unload the above blended material from Octagonal Blender in Poly-lined HDPE Containers and weigh. Calculate Net Weight = Gross Weight – Tare Weight. Affix status label with Product Name, Batch No., Batch Size, Mfg. Date, Exp. Date, Tare Weight, Gross Weight and Net Weight.

STEP – XIII: 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 status label. Continue the compression with 27 stations (D-Tooling) Compression Machine under controlled environmental conditions.

STEP – II: Send composite sample of compressed tablets (Qty. 30 tablets) to QC department for analysis.

STEP – III: Transfer compressed tablets to five Poly-lined HDPE Containers (capacity: 45 liter each). Calculate Net Weight = Gross Weight – Tare Weight. Affix status label.

STEP – IV: After completion of compression, clean the Compression Machine as per cleaning SOP.

6.3 COATING

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

STEP – I (SEAL COAT MATERIALS):

STEP – II (FILM COAT MATERIALS):

COATING EQUIPMENTS:

STEP – IV (PREPARATION OF SEAL COAT SOLUTION) FOR LOT-I & LOT-II:

Take Isopropyl Alcohol IP (10.200 liter) and Dichloromethane USP (24.000 liter) in SS Container (capacity: 45 liter) and add Instacoat Solution White (ICS-223) Non Aqueous (1.800 kg), mix together by Portable Stirrer continuously stirring till uniform mixing achieved. Mixing Time: 20 minutes (To be validated in next batch). Filter with Filter Cloth 100# in SS Container (capacity: 45 liter). Divide the solution (36.000 liter) equally into two parts (18.000 liter) for LOT-I and LOT-II.

STEP – V (SEAL COATING PROCEDURE) FOR LOT-I:

Coating will be done in two lots. Divide total compressed tablets into two equal quantities for LOT-I and LOT-II (90.00 kg tablets for each lot). Load tablets in coating pan (Capacity: 42″), start hot air blower, set inlet air temperature at 70°C to 75°C, warm the tablet bed to 40°C to 45°C.

STEP – VI (PREPARATION OF FILM COATING SOLUTION) FOR LOT-I & LOT-II:

Take Purified Water IP (18.000 liter) in SS Container (capacity: 30 liter) and add Sheffcoat PVA Orange 5Y02059 (4.500 kg). Mix together by Portable Stirrer continuously stirring till uniform mixing achieved. Mixing Time: 20 minutes (To be validated in next batch). Filter with Filter Cloth 100#. Divide the coating solution (22.500 liter) equally into two parts (11.250 liter) for LOT-I and LOT-II.

STEP – VII (FILM COATING PROCEDURE) FOR LOT-I:

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

STEP – IX: Send composite sample of coated tablets (Qty. 30 tablets of each Lot) to QC department for analysis.

STEP – X: Transfer coated tablets to five Poly-lined HDPE Containers (capacity: 45 liter each). Calculate Net Weight = Gross Weight – Tare Weight. Affix status label.