SOP for Tablet Compression and Granulation, the process of particle enlargement by agglomeration technique, is one of the most significant unit operations in the production of pharmaceutical dosage forms, mostly tablets and capsules. SOP for Tablet Compression and Granulation process transforms fine powders into free-flowing, dust-free granules that are easy to compress.

PURPOSE:

To lay down the procedure for Tablet Compression and Tablet Granulation.

SCOPE:

This SOP is for all the processes from compression including the changeover for the next batch at the Production department and granulation including processing for the next batch at the Production department.

RESPONSIBILITY:

1. Execution: Operator.
2. Checking: Production Pharmacist.

REFERENCES:

1. In-house.

PROCEDURE:

COMPRESSION:

1. After cleaning the compression machine as per respective SOP, clean the compression area, dust extractor and its pipe, racks, door frames, diffusers and return grills & filters of Air Handling Unit.
2. While fitting the return filters, check it visually for intactness and absence of leakage.
3. Intimate Q.A department to collect swab samples/rinse water as per requirement.
4. After receiving the approval from quality control department put ‘Cleaned label’ to all the equipment.
5. If machine is to be kept idle then the turret of the machine is to be covered with a thin layer of food grade oil with status label ‘to be cleaned’.
6. It is to be cleaned with 70% isopropyl alcohol before taking clearance from Q.A department.
7. If the compression of the product is to be started, remove the ‘cleaned’ status label and affix the status label to the machine along with product name & Batch details, which is to be compressed.
8. Issue the punch set suitable for the product to be compressed as per the description of the punch set in the compression record of the batch manufacturing and as per SOP.
9. Fill up the punch tool record with all the details of the punch set issued, on the punches & dies Log Book.
10. Set the compression machine as per SOP and check the setting of the machine by rotating hand wheel.
11. Bring all the containers of lubricated granules of respective batch along with the batch manufacturing record to the area. Counter check the labels of all the containers for correct batch details as per the batch manufacturing record.
12. Set the machine as per the tablet parameters given in batch manufacturing record.
13. Destroy the tablets of first few rotations before starting the machine for the compressions of the batch as per the SOP.
14. Collect the tablets generated during machine setting in a cleaned, polythene lined container and keep it duly labeled and packed.
15. At the end of the compression, when the material in the hopper reaches to the lowest level stop the compression and destroy the left over from the feed frame or use it as an Utilizable residue.
16. After completion of the compression of the batch weigh the containers of the compressed tablets and record it in the batch manufacturing record and do reconciliation as per BMR.
17. Clean all the containers from outside and transfer it to in-process qurantine with the label having all batch details. And enter it in the In-process Qurantine Log Book.
18. If next batch of same product is to be takenfollows the above steps from 5 to 17.
19. If the batch of the new product is to be taken for compression remove all the left over materials and record of the previous batch from the area and put “To be cleaned” label to all equipment and area.
20. Remove the punch sets and record the same in punch tool record. Clean the punch set as per respective SOP and store the punch set in punch storage area.
21. At the time of setting and checking the in process parameters of the tablet assure the I.P.Q.C.
    a) Ensure that equipments like hardness tester, friability test apparatus and Vernier caliper are calibrated.
    b) For disintegration test use fresh water every time and discards the previously used water.

WET GRANULATION:

1. After getting the line clearance from QA person for the area and for the equipment, bring the dispensed material of the batch to the manufacturing area by checking and assuring that the balance is calibrated. Then check all the ingredients for name, weight and batch number against the Manufacturing order and sign on the received column of MO and dispensed slip.
2. Check and record temperature, relative humidity and pressure differential in the area at the time of line clearance.
3. During material handling and carrying out the manufacturing process, the operator should wear mask and gloves.
4. Flush first few liters of the purified water and collect and use fresh purified water for the manufacturing process after rinse test.
5. Check all the equipment for proper assembly and run it in empty condition to check for friction or abnormal sound or presence of foreign material, if any of the abnormalities observed, inform the maintenance, get it rectified and re-clean the equipment after maintenance.
6. Check intactness of the screen & sieves before & after completion of the work.
7. Refer the instructions given in the batch manufacturing record and make all the entries timely in good and clean handwriting.
8. Avoid the overwriting while making the entries in the batch manufacturing record. In case of any error it is to be cut with single line and to be re-entered with counter sign and date.
9. Any deviation during manufacturing process should be immediately informed to Production Manager and Q.A person.
10. No material should be kept on the floor or unlabeled during the manufacturing process.
11. The required cleaned empty utensils should be kept in area for carrying out the manufacturing operation.
12. After completion of sieving of the material should be added in the U-type mixer as per the sequence given in the batch manufacturing record.
13. Operate the Rotary wet granulator as per SOP, during milling operation, check the appearance of discharge material as per requirement of individual products.
14. Operate the oscillating as per respective SOP. Granulate the material as per instruction given in BMR.
15. After achieving the end point of the granulation the time and other details should be recorded for wet mixing in the batch manufacturing record.
16. Operate the oven tray dryer as per SOP. Any damage if observed should be reported to Production Manager.
17. Before lubrication, check the weight of dried granules. Lubricate the batch as per instruction given in BMR.
18. After completion of the manufacturing process, unloaded material should be checked for proper labeling, closing of the bags and the lids of the container before sending it to storage area.
19. After completion of the manufacturing activity, the Operational log book is to be entered with all the details including stoppage of activity and equipment breakdown if any in “Operational Log Book & Maintenance Log Book”.
20. The equipment stoppage during the manufacturing activity should be immediately informed to Production Manager and maintenance department.
21. After repairing of the instrument/ equipment the line clearance is to be taken from quality assurance person to restart the activities and recalibration of the same should be carried out if applicable.
22. If the manufacturing of the new products is to be carried out in the same area follow the standard operating procedure for change over as per the SOP.
23. Remove all the documents, left over material and status label of the previous product from the area.
24. Put “To be Cleaned” label on all equipments and area.
25. Remove all the deposited material from the electrical parts like motor, panel and switches and cover with poly bags.
26. Clean all the equipments as per standard cleaning procedure.
27. Clean the grills & return Air filters of HVAC.
28. Before fitting check the filter for cleanliness, intactness and absence of leakage, if any, record the same in respective records.
29. Clean door frame, walls, tables, tube light covers and floors and filters of return air supply ducts.
30. After completion of cleaning check all the equipment and the area for cleanliness and give intimation to Q.A officer to collect swab samples/ rinse water samples.
31. The filled containers should be stored in storage area in segregation.
32. The pellets and the drums in the storage area should be in clean condition.
33. The recoverable residue if any should be entered in recovery register.