Formula Master: Aceclofenac 100 mg and Paracetamol 325 mg Tablets

Formula Master: Aceclofenac 100 mg and Paracetamol 325 mg Tablets

Source: drugsformulations.com via archive.org

Product Name: Aceclofenac 100 mg and Paracetamol 325 mg Tablets

Aceclofenac 100 Mg And Paracetamol 325 Mg Tablets

Sumber: drugsformulations.com via archive.org

MFR of Aceclofenac 100 mg and Paracetamol 325 mg Tablets

Page No

PRODUCT DETAILS

MANUFACTURING FORMULA

MANUFACTURING INSTRUCTIONS

GENERAL PRECAUTIONS

MANUFACTURING PROCESS DETAILS

GRANULATION

COMPRESSION

COATING

1.0 PRODUCT DETAILS:

Product Name

Aceclofenac and Paracetamol Tablets

Product Description

Orange color, elongated biconvex, film coated tablet having one side mid break line and other side plain

Strength

Aceclofenac 100 mg and Paracetamol 325 mg

Label claim

Each film coated tablet contains:

Aceclofenac IP – 100 mg

Paracetamol IP – 325 mg

Batch Size

3,00,000 Tablets

Average Weight

580 mg

Shelf Life

24 months

Storage

Store in a cool, dry and dark place below 25 0 C

Drug Category

Anti-Inflammatory Drug

2.0 MANUFACTURING FORMULA:

Material Name

Category

Quantity per Unit (In mg)

Overages

Batch Qty.  (In kg)

Dry Mixing

Aceclofenac

100 mg

30.000 kg

Paracetamol

325 mg

97.500 kg

Starch

Diluent

50.00 mg

15.000 kg

MCCP Plain

Diluent

61.59 mg

18.477 kg

Binder

PVPK-30

Binder

0.900 kg

Sodium Benzoate

Preservative

1.16 mg

0.348 kg

Gelatin

Binder

0.900 kg

Starch

Binder

16.25 mg

4.875  kg

Purified Water

Solvent

0.160 ml

48.000 liter

Lubricant

Talcum

Anti-caking agent

3.000 kg

Sodium Starch Glycolate

Disintegrants

2.400 kg

Magnesium Stearate

Anti- Adherent

0.600 kg

Sr. No.

Machineries/equipments

Capacity

Equipment ID.

Weighing Balance

300 kg ,100 kg

Sifter (with SS Sieves No’s 16,20,30,60 and 100)

Paste Kettle with stirrer

60 liter

Stirrer for binder preparation

Multi-Mill (screen size 8 mm, 2 mm)

Rapid Mixer Granulator (RMG )

160 liter

Fluid Bed Dryer (FBD)

120 kg

Octagonal Blender

500 liter

Compression Machine

27 Station

SS Containers with lid

10 liter,30 liter and 100 liter

Halogen Moisture Balance

Poly-lined HDPE Containers with lid

30 liter and 45 liter

4.0 MANUFACTURING INSTRUCTIONS:

Aceclofenac API Description: A white or almost white crystalline powder.

Paracetamol API Description: A white crystals or a white crystalline powder.

All the manufacturing activities shall be performed under controlled conditions (temperature NMT 25 0 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 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:

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

Aceclofenac IP

30.000 kg

Paracetamol IP

97.500 kg

Starch IP

15.000 kg

MCCP Plain IP

18.477 kg

Binder

PVPK-30 IP

0.900 kg

Sodium Benzoate IP

0.348 kg

Gelatin IP

0.900 kg

Starch IP

4.875 kg

Lubricant

Talcum IP

3.000 kg

Sodium Starch Glycolate IP

2.400 kg

Magnesium Stearate IP

0.600 kg

Collect the sifted Aceclofenac IP (30.000 kg), Paracetamol IP (97.500 kg), Starch IP (15.000 kg) and MCCP Plain IP (18.477 kg) into four Poly-lined HDPE Container (capacity: 45 liter each) two equal parts for LOT I and LOT II.

Collect the sifted Starch IP (4.875 kg) in SS Container (capacity: 10 liter)

Collect the sifted Talcum IP (3.000 kg) and Sodium Starch Glycolate IP (2.400 kg) in Poly-lined SS Container (capacity : 10 liter)

Collect the sifted Magnesium Stearate IP (0.600 kg) in Poly-lined SS Container (capacity: 10 liter)

Divide the sifted material Aceclofenac IP (30.000 kg), Paracetamol IP (97.500 kg), Starch IP (15.000 kg) and MCCP Plain IP (18.477 kg) in two equal parts for LOT-I and LOT-II.

STEP – II (DRY MIXING): FOR LOT – I:

Transfer the sifted Aceclofenac IP (15.000 kg ), Paracetamol IP (48.750 kg ), Starch IP (7.500 kg) and MCCP Plain ( 9.238 kg ) in RMG ( capacity : 160 liter) and dry mix the materials till uniform mixing.

Mixing Time = 8 minutes.

Mixing Speed: 03 minutes at slow speed and 05 minutes at fast speed.

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

(a) Take purified water (42.00 liter) in Paste Kettle, heat the purified water at 80 0 C and add Gelatin IP (0.900 kg).

(b) Take purified water (5.00 liter, at temperature 25 0 C) in SS Container (capacity: 30 liter) and add Starch IP (4.875 kg) slowly with continuously stirring till uniform solution is ready.

(c) Add the above solution of Step – III (b) in solution of Step – III (a) in Paste Kettle with continuously stirring till uniform paste is ready.

(d) Take purified water (1.000 liter, at temperature 35°C) separately in SS Container (capacity: 10 liter) and add 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 then add to Step – III (c) and continuously stirring till final paste is ready and cool the paste to 35°C to 40°C.

(e) Divide paste into two equal parts for LOT – I and LOT – II in SS Containers (capacity: 30 liter each).

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

Slowly add the binder of Step-III in dry mix materials of Step – II in Rapid Mixer Granulator (capacity: 160 liter) with running at slow speed impeller (13 ampere) for 5 minutes. Then run impeller and chopper both at medium speed (15 ampere) for 10 min and finally run both chopper and impeller on fast speed (19 ampere) for 3 minutes till uniform mixing. Unload the material in SS Container (capacity: 100 liter) from RMG.

Mixing Time: 18 minutes

Ampere Load of Impeller: 13 to 19 ampere.

STEP-V (WET SCREENING) : FOR LOT – I:

Take wet material from SS Container (capacity: 100 liter) and pass through Multi-Mill with 8 mm screen and collect the wet material in a FBD bowl.

STEP –VI – (DRYING) : FOR LOT- I:

Dry the wet material of Step-V in FBD (capacity: 120 kg) till the LOD of granules is achieved between 2.5 to 3.0 % at 105°C checking by Halogen Moisture Balance.

Inlet Temperature: 55°C.

Outlet Temperature : To be established

Bed Temperature: To be established

Raking Frequency: After 30 minutes

Drying Time: 2 hours.

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

Check Screen Integrity (before sifting and after sifting).

Milled the dried material of Step -VI through Multi Mill using screen size 2 mm and collect milled material in one SS Containers (capacity :100 liter ). After milling transfer the milled material into four 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

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 (PRE –LUBRICATION):

Load the milled granules of Step-VII of LOT- I and LOT – II in Octagonal Blender (capacity: 500 liter) and add sifted Talcum IP (3.000 kg) and Sodium Starch Glycolate IP (2.400 kg), mix properly till uniform mixing of Pre-Lubricating Material.

Mixing Time: 30 minutes (15 minutes clockwise direction and 15 minutes anti-clockwise direction)

Mixing Speed: 10 RPM

STEP – IX (LUBRICATION):

Add the sifted Magnesium Stearate IP (0.600 kg) in Step-VIII 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- X (BLEND SAMPLE ANALYSIS):

After completion of lubrication, collect the composite blend sample and send to QC for analysis according to the table below:

Specification

Appearance of blend

Blend Uniformity

Blend Assay

Bulk Density

Tapped Density

Compressibility Index

Hausner Ratio

White color free flowing granular powder

90 % to 110 %

98 % to 103 %

2.0 % to 3.0 %

0.7692 gm/ml

0.9677 gm/ml

20.3788 % (Fair)

1:2581 (Fair)

STEP – XI:

Unload the above blended material and weight and store in seven Poly-lined HDPE Containers (capacity: 30 liter each).

STEP – XII:

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

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.

Parameters

Standard

No. of Tablets

In-Process Frequency

Feed frame alignment and adjustment

Should be satisfactory

Lower Weight Assembly

Should be satisfactory

Hydraulic Pressure

6 -8 Tones (D-Tooling, 27station Compression Machine)

Machine Speed

15 RPM to 18 RPM

Upper Punch Size

15 mm with break line

Lower Punch Size

7.5 mm

Length of Tablets.

Width of Tablets

7.5 mm

6/Individual

2 hours

Thickness of Tablets

6.61  mm ±.2 mm

6/Individual

2 hours

Weight of 20 Tablets

11.600 gm. ± 3%

20/Composite

30 minutes

Product Description

White color, elongated biconvex, uncoated tablet having one side mid break line and other side plain

20/Composite

2 hours

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

Average Weight of Tablets

580 mg ± 2 %

20/Individual

30 minutes

Hardness

NLT 4 kg/cm 2

6/Individual

30 minutes

Disintegration Time

NMT 15 min

6/Composite

01 hour

Friability

NMT 1%

20/Composite

01 hour

STEP – II:

Send the sample of compressed tablets to QC department for analysis.

STEP – III:

Weight the compressed tablets and store into seven Poly-lined HDPE Containers with lid (capacity: 30 liter each) with proper status label till next step tablet packing.

STEP – IV:

Clean the Compression Machine as per cleaning SOP.

COATING:

STEP – I (COATING MATERIALS DETAILS):

Sr. No.

Material Name

Batch Quantity (In kg)

Sheffcoat PVA Orange 5Y02059

4.350 kg

Purified water IP

17.400 liter

Sr. No.

Machineries/Equipments

Capacity

Equipment ID.

Coating Pan

Spray Gun

1.5 mm

Filter Cloth 100 #

0.5 mm

Stirrer

SS Container

30 liter (03 no’s)

Poly-lined HDPE Containers with lid

30 liter (07 no’s)

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

Take Purified Water IP (17.400 liter) and mix Sheffcoat PVA Orange 5Y02059 (4.350 kg) in SS Container (capacity: 30 liter) and mix properly with stirrer till uniform mixing achieved.

Speed of stirrer: Constant.

Filter the coating solution with Nylon Filter Cloth 100# (0.5 mm).

Keep the solution for 30 minutes and after 30 minutes proceed for coating process.

Divide the coating solution equally into two parts for LOT – I and LOT – II in SS Container (capacity: 30 liter each)

STEP – IV (COATING PROCEDURE OF TABLETS): FOR LOT- I:

Coating will be done in two lots, divide total compressed tablets into two equal quantities for LOT -I and LOT -II (87.000 kg tablets for each lot).

Load the tablets of LOT – I (87.000 kg) in coating pan (capacity: 42″), start the hot air blower, set the supply air temperature at 60°C to 65°C and start the exhaust fan & warm the tablets bed 40°C to 45°C.

After warm up of tablets, take weight of 100 warm tablets for calculation of weight buildup of tablets after coating.

Set the coating parameter as given in below table and start the coating process by starting coating spray from gun.

Parameter

Specification

Status

No. of Baffles in coating pan

No. of Guns

Gun to Gun Distance

08 inch

Gun to Tablet Bed Distance

10 inch

BED Temperature

40 0 C to 45 0 C

Pan RPM

18 to 22 rpm

% Weight Gain

2.0 %

STEP – V (COATING IN-PROCESS CHECK PARAMETERS): FOR LOT- I:

Parameters

Standard

No. of Tablets

In-Process Frequency

Product Description

Orange color, elongated  biconvex, film coated tablet having one side mid break line and other side plain

20 No.

After batch completion

Weight of 20 Tablets after coating

11.832 gm. ± 2 %

20 No.

Average Weight after coating

591.6 mg ± 2%

20 No.

Individual Tablets Weight Variation

20 No.

Thickness

6.63 mm ± 0.2 mm

Disintegration

NMT 30 min.

FOR LOT – II (COATING PROCEDURE): Please follow the same procedure of LOT – I of coating from Step-IV and Step -V.

STEP – VI:

Send the composite sample of coated tablets of LOT- I and LOT – II to QC department for analysis.

STEP – VII:

Weigh the coated tablets and store the coated tablets into seven Poly-lined HDPE Containers with lid (capacity: 30 liter each) with proper status label till next step tablet packing.

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