SILDENAFIL CITRATE TABLETS

PURPOSE: 

This MFR is written to describe the formulae, manufacturing procedure, specifications, packing details of dosage form.

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

RESPONSIBILITY / ACCOUNTABILITY:

It is the responsibility of Assistant Manufacturing Chemist to follow and adhere to this MFR. 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 

 COMPOSITION: 

Each film coated Tablet contains:

Sildenafil Citrate

Equ. To Sildenafil                                             100 mg

EQUIPMENTS TO BE USED:

RAW MATERIAL:-

PACKING MATERIAL:

MANUFACTURING SPECIFICATION:

1. Moisture content of powder should be less than 2.0 %.
2. Average weight of each Tablet is 350 milligrams.
3. Weight Variation Limit for average weight of 20 tablets is +0%.
4. Friability limit for 20 Tablets is not more than 1.0 %.
5. Hardness of the Tablets varies between 2 – 4 kg/cm².
6. Disintegration time for each Tablet is not more than 30 minutes.
7. Mix the batch, compress and de-dust the tablets and also perform the primary packing of Tablets at temperature not more than 25˚C.

Yield:

• Theoretical Yield is 1.0 Lac Tablets.
• Expected Practical Yield is 1.0 Lac + 2% Tablets.

      Packing Details:

1. Use PVC 104 mm Clear and Aluminium foil for blister packing.
2. Blister Pack the inspected and coated tablets by using Single Track Blister Packing Machine as per its SOP.
3. Put 10 strips each containing 3 tablets in each carton.
4. Seal the each carton from both ends with cello tape.
5. Pack such 10 cartons in specified in each outer carton
6. Pack such 63 outer cartons to give a pack size of 63 x 10 x 3 tablets.
7. Seal the each corrugated box with adhesive tape and label it properly by affixing the specified label.

       MANUFACTURING PROCESS:

1. Preparation of Starch Paste:

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

• Dissolve 0.050 kg of Sodium Benzoate in 0.5 Ltrs of DM water and stir continuously.
• Add 0.720 kg of Starch in 1.0 Lts D.M. water and stir continuously to make smooth slurry.
• To this 20 Ltr. of D.M water add the solution of sodium benzoate and starch slurry with constant stirring to get a uniform paste.
• Preparation of binder: Prepare the binder by dissolving 0.200 kg of pvpk30 in3.650 kg of isopropyl alcohol.

2. Sifting:

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

3. 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.

• 12.750 kgs of Dicalcium Phosphate.
• 3.200 kgs of Lactose
• 2.800n kgs of M.C.C.P

4. 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 to the blended powder in a manner so as to achieve proper wetting. Mix the Sildenafil Citrate with binder in isopropyl alcohol & pvpk30 in Rapid Mixer Granulator.

5. 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.

6. 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 achieve room temperature.

7. Sifting:

Fit the mesh # 14 Stainless Steel Sieve on the Sifter-II as per its SOP . Sift all granules 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.

8. Check the total weight of dried granules. Determine the loss on drying and percentage yield of dried granules.

9    Lubrication:

Lubricate the sifted granules and above compacted material together along the following ingredients in Roto Cube Blender by operating it as per its SOPI for 15 minutes and collect in Stainless Steel Container.

• 0.500 kgs of Magnesium Stearate
• 0.500 kgs of Talcum
• 0.500 kgs of Sodium Starch Glycolate
• 0.500 kg of Aerosil

10. Send the granules for bulk testing to Quality Control Department for assay of Active Ingredients.
11. 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. 

12. Tablet Inspection:

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

13. Coating of the tablet:

 Dissolve 1.120 kgs of Instacoat sunset yellow in 7.80 kgs of Isopropyl Alcohol. Then add 16.70 kgs of Methylene chloride to this solution. Collide this solution by Colloidal Mill as per SOP. Now start coating of the tablets by using Rapid Cota Tablet Coating Machine by operating it as per its SOP and collect the coated tablets in Stainless Steel Container.

14. Tablet Inspection:

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

15. 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:

1. Check Raw materials used for manufacturing purpose are all approved materials and have ‘Released’ labels fixed on it.
2. All weighed Raw materials should be counter-checked by Assistant Manufacturing Chemist. If any discrepancy is noticed, it should be immediately brought to the notice of Production Pharmacist and QC/QA Manager.
3. Physical characteristics of Raw material like colour, odour, and consistency are checked before compounding.
4. Humidity and temperature should be maintained during the compression of thermolabile products.
5. Sample of dried granules should be sent to Quality Control Department for the determination of Moisture content.
6. The total weight of blended powder should be checked in the presence of Assistant Manufacturing Chemist and record the same in Batch Manufacturing Record.
7. Bulk sample should be sent for analysis to Quality Control Department before starting compression of tablets.
8. 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:
9. 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:

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

iii) 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.

1. iv) 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.
2. v) Re-check the weight of tablets for further adjustment, if any.
3. 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.

10. 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.

11. 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%

12. Disintegration Test:

i) 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.

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

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

iv) 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.

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

vi) 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.

vii) 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.

viii) 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

13. Tablets taken for testing and In-process control should not be added to the bulk batch to avoid mix-ups and cross-contamination.
14. Inspection, sorting of rejected tablets should be done as per SOP.
15. The strips and cartons should be checked thoroughly for proper batch coding.

16. Assistant 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.
17. Intimation should be sent to Quality Control Department for finished product sampling and testing.
18. 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.
19. It will be ensure that filling or packaging equipment has been properly cleaned after the completion of batch.
20. Filling or packaging of next product should not commence until the IPQA has given the ‘Line Clearance’.