MFR of Paracetamol & Dicyclomine HCl Tablets

MFR of Paracetamol & Dicyclomine HCl Tablets

PURPOSE: This Master Manufacturing Record (MFR) is written to describe the formulae, manufacturing procedure, specifications, packing details of dosage form.

SCOPE: This MFR is performed and is applied during the manufacturing of dosage form.

RESPONSIBILITY / ACCOUNTABILITY: It is the responsibility of Manufacturing Chemist to follow and adhere to this SOP. The Production Pharmacist, QC/QA Manager are accountable for the strict adherence to the master formula.

COPY ISSUED TO:

  1. Master Copy: Manager Quality Assurance
  2. Copy No. 1: Production Pharmacist
  3. Copy No. 2: Manager Quality Control
  4. Copy No. 3: Tablet Section
PRODUCT NAME: Paracetamol & Dicyclomine HCl Tablets BATCH SIZE:  10.0 LACS
PRODUCT REFERENCE CODE:  UNIT SIZE:  20 x 10
GENERIC NAME: N. A. PACK SIZE:  68 x 20 x 10
DOSAGE FORM: TABLET STRENGTH: N.A.
DEPARTMENT:  TABLET DEPARTMENT EXPIRY DATE: AFTER 24 MONTHS     FROM THE DATE OF MANUFACTURING

 COMPOSITION:

 Each uncoated Tablet contains:

Dicyclomine HCl                                    I.P.              20 mg

Paracetamol                                             I.P.             500 mg

EQUIPMENTS TO BE USED:

SR. NO. NAME OF EQUIPMENT ASSEMBLING

AS PER SOP NO.

  CLEANING

AS PER SOP NO.

1 Steam Jacketed Starch Paste Preparation Tank    
2 Sifter Machine – I    
3 Roto Cube Blender –I    
4 Rapid Mixer Granulator    
5 Multi Mill    
6 Fluidized Bed Drier    
7 Oscillating Granulator    
8 Sifter Machine – II    
9 Roto Cube Blender – II    
10 Tablet Compression Machine 27 Stations    
11 Dedusting Machine    
12 Tablet Inspection Machine    
13 Single Track Blister Packing Machine    

RAW MATERIALS:-

S.NO. INGREDIENTS STD Theoretical Quantity Req. Overages % Total Quantity Used
1. AEROSIL    B.P 1.500   1.500 kgs
2. D.C.P I.P 21.500   21.500 kgs
3. DICYCLOMINE HCL I.P 20.000   20.000 kgs
4. S.S.G I.P 7.330   7.330 kgs
5. LACTOSE I.P 1.400   1.400 kgs
6. M.C.CP B.P 14.300   14.300 kgs

 

7. MAGNESIUM STEARATE I.P 4.300   4.300 kgs
8. PARACETAMOL I.P 500.000   500.000 kgs
9. PVPK – 30 I.P 4.000   4.000 kgs
10. SODIUM BENZOATE I.P 2..830   2.830 kgs
11 STARCH     I.P 28.300   28.300 kgs
12 STARCH I.P 21.660   21.660 kg
13 TALCUM I.P 0.360   0.360

PACKING MATERIALS:-

S.NO. NAME OF THE MATERIAL Theoretical Quantity Req. For

Record

Total Quantity Used
1. 104 MM LIGHT GREEN (PVC) 130.000   130.000 KGS
2. ADHESIVE TAPE ROLL BROWN 2.000   2.000 NOS
3. CELLO TAPE 6.000   6.000 NOS
4 BLISTER FOIL

(SPAS TABS)

30.000   30.000 KGS
5 CORRUGATED BOXES   S – 11 73.000   73.000 NOS
6 UNIT CARTON  – 20 X 10

(SPAS TABS)

5000.000 2.000 5002.000 NOS

MANUFACTURING SPECIFICATION:

Moisture content of powder should be less than 2.0 %.

Average weight of each Tablet is 645

Weight Variation Limit for average weight of 20 tablets is +0%.

Friability limit for 20 Tablets is not more than 1.0 %.

Hardness of the Tablets varies between 2 – 4 kg/cm2.

Disintegration time for each Tablet is not more than 15 minutes.

Mix the batch, compress and de-dust the tablets and also perform the primary packing of Tablets at temperature not more than 250

Yield:

Theoretical Yield is 10.0 Lacs Tablets.

Expected Practical Yield is 10.0 Lacs + 2% Tablets.

Packing Details:

Use PVC 104 mm Light Green and Aluminium foil for blister packing.

Blister Pack the inspected and De-dusted tablets by using Single Track Blister Packing Machine as per its SOP.

Put 20 strips each containing 10 tablets in each carton.

Seal each carton from both ends with cello tape.

Pack 68 unit cartons in specified corrugated box S-11 to give a pack size of 68 x 20 x 10 tablets.

Seal each corrugated box with adhesive tape and label it properly by affixing the specified label.

MANUFACTURING PROCESS:

Preparation of Starch Paste:

Prepare the starch paste two lots:

Prepare the starch paste in the manner given below using Steam Jacketed Starch Paste Preparation Tank by operating it as per its SOP.

Dissolve 0.750 kgs of Sodium Benzoate in 2 Ltrs of DM water and stir continuously.

Add 10.83 kgs of Starch in 11 Ltrs D.M. water and stir continuously to make slurry.

To 80 Ltrs of boiling water add the solution of sodium benzoate and starch slurry with constant stirring to get a uniform paste.

Repeat the same process for next of the lot.

Sifting:

Fit the mesh # 40 Stainless Steel Sieve on the Sifter-I as per its SOP. Sift all granules through it and collect separately in Stainless Steel Containers.

Blending:

Blend the following ingredients using Roto Cube Blender by operating it as per its SOP for 60 minutes and collect in Stainless Steel Containers.

  • 10.75 kgs of Dicalcium Phosphate.
  • 0.7 kgs of Lactose
  • 7.15 kgs of M.C.C.P.
  • 250.0 kgs of Paracetamol

Repeat the same process for next lot with same quantity mentioned above.

Wet Granulation:

Mix the above blended ingredients with the Starch paste using Rapid Mixer Granulator by operating it as per its SOP. Add starch paste in such a manner by following the procedure given below so as to achieve proper wetting.

Divide the total blended powder in twenty equal parts.

Divide the prepared starch paste in twenty equal parts.

Mix the one part of blended powder and starch paste together in Rapid Mixer Granulator.

Similarly mix the other parts in same manner.

Wet Screening:

Pass the wet dough through a Multi Mill by operating it as per its SOP to convert the moist mass into coarse, granular aggregates.

Drying:

Dry the granules in Fluidized Bed Drier by operating it as per its SOP at temperature 600 – 700 C for 30 minutes. Cool the granules to room temperature.

Sifting:

Fit the mesh # 14 Stainless Steel Sieve on the Sifter-II as per its SOP. Sift the all ingredients through it and collect in Stainless Steel Container. Break the oversized granules left over the mesh in Oscillating Granulator by operating it as per its SOP and resift them.

Check the total weight of dried granules. Determine the loss on drying and percentage yield of dried granules. Divide the granules in two equal lots. 

Lubrication:

Lubricate one lot of the sifted granules along the following ingredients through Roto Cube Blender by operating it as per its SOP for 15 minutes and collect in Stainless Steel Containers.

  • 0.750 kgs of Aerosil
  • 2.150 kgs of Magnesium Stearate
  • 3.665 kgs of S.S.G
  • 0.180 kgs of Talcum
  • 10.0 kgs of Dicyclomine HCl

Repeat the same process for rest of the lots with same quantity mentioned above.

Send the granules for bulk testing to Quality Control Department for assay of Active Ingredients.

Compression:

Shift all the granules for compression to Tablet Compression Machine 27 Stations by operating it as per its SOP and collect the compressed tablets in Stainless Steel Container.

Tablet Inspection:

Transfer the all tablets to tablet inspection machine and sort out the defected tablets by operating it as per its SOP  and collect the selected tablets in Stainless Steel Container.

Blister Packing:

Shift the inspected tablets to blister section and blister pack them using Single Track Blister Packing Machine by operating it as per its SOP.

IN-PROCESS CONTROLS:

 The following in-process controls should be maintained during the processing:

Check Raw materials used for manufacturing purpose are all approved materials and have ‘Released’ labels fixed on it.

All weighed Raw materials should be counter-checked by Manufacturing Chemist. If any discrepancy is noticed, it should be immediately brought to the notice of Production Pharmacist and QC/QA Manager.

Physical characteristics of Raw material like colour, odour, and consistency are checked before compounding.

Humidity and temperature should be maintained during the compression of thermolabile products.

Sample of dried granules should be sent to Quality Control Department for the determination of Moisture content.

The total weight of blended powder should be checked in the presence of Assistant Manufacturing Chemist and record the same in Batch Manufacturing Record.

Bulk sample should be sent for analysis to Quality Control Department before starting compression of tablets.

Weight Variation: I) Intermittently weight variation of compressed tablets should be checked at 30 minutes interval by the Assistant Manufacturing Chemist and record for the same should be kept in Batch Manufacturing Record.

Out-of-limit tablets should be checked by Weight Variation Method as given below:

Take the average weight of 20 tablets on the calibrated balance and calculate the upper and lower limit as per the table given below in accordance with IP/BP:

AVERAGE WEIGHT OF TABLETS
                 (in mg)
  MAXIMUM PERCENTAGE DIFFERENCE                                                                      ALLOWED
80mg or less                                10
More than 80mg and less than 250mg                                 7.5
250mg or more                                  5

Take the weight of individual tablets and check if all the tablets are lying with in the limits.

Select the tablets only if no more than two tablets are out of percentage limit and if no tablet differs by more than two times the percentage limit, otherwise reject the tablets.

Adjust the desired weight of the tablets in the Compression Machine by moving weight adjustment cam clockwise or anticlockwise accordingly as per the Standard Operating Procedure of Compression Machine.

Re-check the weight of tablets for further adjustment, if any.

Thickness of Tablets: Thickness of the tablets should be determined by means of the vernier caliper. The thickness of the tablet should be checked whenever weight adjustments are made.

Hardness of the tablets: The equipment used is the ‘Monsanto’ type hardness tester. Hardness of the compressed tablets should be checked at regular interval to determine the need for pressure adjustments on the tableting machine.

Hardness of tablets varies between: 2-4 Kg/cm2.

Friability:

‘Roche Friabilator’ is used for measuring the Friability. The instrument is designed to evaluate the ability of the tablet to withstand abrasion in packaging, handling and shipping.

Adjust the instrument to 25 RPM before adding the tablets.

Weigh 20 Tablets on calibrated balance. Transfer the tablets in the plastic chamber. Close the drum tightly.

Switch on the apparatus. Operate the Friabilator for 100 revolutions.

De-dust and reweigh the tablets. Loss in weight indicates the ability of tablets to withstand the wear.

Take 10 tablets to check the friability, when the average weight of tablet is 1g or more than 1g.

Friability Limit  = Less than 1.0%

Disintegration Test:

Disintegration is the time required for the group of tablets to disintegrate into the particles. Disintegration Test should be carried out at regular interval of 1 hour by using Disintegration Test Apparatus.

The tube assembly unit is removed from the glass beaker and from each tube the plastic discs are removed.

Place the tablets in each of 6 tubes along with a plastic disc over the tablets.

The glass beaker is filled with water. The water in the beaker is retained at the temperature of 37+1˚C through out the test by suitably setting the thermostat.

Introduce a tube assembly unit into glass beaker in such a way that wire mesh at the base of each tube is at least 2.5cm below the surface of liquid when the basket is at highest position.

Switch on the apparatus to move the basket assembly containing the tablets up and down through a distance of 5 to 6 cm at a frequency of 28 to 32 cycles per minute. Start the stopwatch.

When the tablets have disintegrated i.e. when no particles remain on the wire mesh at the bottom of tube, stop the stopwatch. Note the time taken for disintegration of the tablets and record the same in Batch Manufacturing Record.

If one or two tablets fail to disintegrate, the test is to be repeated using 12 tablets.

Disintegration Time of uncoated tablets= Not more than 15 minutes

Disintegration Time of coated tablets= Not more than 30 minutes

Tablets taken for testing and In-process control should not be added to the bulk batch to avoid mix-ups and cross-contamination.

Inspection, sorting of rejected tablets should be done as per SOP.

The strips and cartons should be checked thoroughly for proper batch coding.

Manufacturing Chemist and Production Pharmacist should randomly check that the correct no. of strips are being packed in each cartons and also the number of cartons in each shipper is exactly the same as that shown in proof.

Intimation should be sent to Quality Control Department for finished product sampling and testing.

After the completion of labelling and packaging, the coded cartons should be accounted for and rejected printed material should be destroyed in the presence of QC/QA Manager. Fill the destruction sheet and attach the same in the Batch Manufacturing Record.

It will be ensure that filling or packaging equipment has been properly cleaned after the completion of batch.

Filling or packaging of next product should not commence until the IPQA has given the ‘Line Clearance’.

HEAL GUM PAINT