Nimesulide B.P. 100 mg

Nimesulide B.P. 100 mg

PURPOSE: This Standard Operating Procedure 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 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 :  Non-β Lactam Capsule Section

PRODUCT NAME: Nimesulide B.P. 100 mg

BATCH SIZE:  3.0 LAC
PRODUCT REFERENCE CODE: 233 UNIT SIZE:  20 ´ 10
GENERIC NAME: NIMESULIDE & DICLOFENAC SODIUM CAPSULES PACK SIZE:  60 ´ 20 ´ 10
DOSAGE FORM: CAPSULE STRENGTH: N.A.
DEPARTMENT:  NON β-LACTAM DEPARTMENT EXPIRY DATE:  AFTER 24 MONTHS   FROM THE DATE OF MANUFACTURING

    COMPOSITION:

Each Capsules contains:

Nimesulide                       B.P.    100 mg

    Diclofenac Sodium           I.P.       50 mg

  EQUIPMENTS TO BE USED: 

SR. NO. NAME OF EQUIPMENT ASSEMBLING

AS PER SOP NO.

CLEANING

AS PER SOP NO.

1  Tray Drier Machine    
2  Sifter    
3 Roto Cube Blender    
4 Automatic Capsule Loading Machine    
5 Semiautomatic Capsule Filling  Machine    
6 Feeder, Sorter & Capsule Polishing Machine With A.D.U.    
7 Triple Track Blister Packing Machine    

RAW MATERIALS:

S.NO. INGREDIENTS STD Theoretical Quantity Req. Overages % Total Quantity Used
1 AEROSIL B.P. 0.600   0.600 KGS
2 DI CALCIUM PHOSPHATE I.P. 7.500   7.500 KGS
3 DICLOFENAC SODIUM I.P. 15.000   15.000 KGS
4 EMPTY CAPSULES

GREY / YELLOW  (SIZE: 2)

30000.000   30000.000 NOS
5 MAGNESIUM STEARATE I.P. 2.400   2.400 KGS
6 NIMESULIDE B.P. 30.000   30.000 KGS
7 STARCH I.P. 19.800   19.800 KGS
8 TALCUM I.P. 4.500   4.500 KGS

Packing Material:

S.NO. NAME OF THE MATERIAL THEORETICAL QUANTITY REQ. FOR

RECORD

TOTAL QUANTITY USED
1. 78 MM CLEAR (PVC) 42.000   42.000 KGS
2 ADHESIVE TAPE ROLL BROWN 1.000   1.000 NOS
3 CELLO TAPE 3.000   3.000 NOS
4 ALUMINIUM FOIL 9.000   9.000 KGS
5 UNIT CARTON  (20 X 10) 1500.000 2.000 1502.000 NOS
6 CORRUGATED BOX S – 11 (K-13) 25.000   25.000 NOS

MANUFACTURING SPECIFICATION:

  1. Use number two size Gray/Yellow
  2. Moisture content of powder should be less than 2.0 %.
  3. Average fill of each capsule is 260 milligrams.
  4. Weight Variation Limit for average weight of 20 Capsules is +5 %
  5. Disintegration time for each Capsule is not more than 15 minutes.
  6. Average weight of twenty filled capsules is 6.4 grams.
  7. Mix the batch, Fill and Polish the Capsules and also perform the primary packing of Capsules at temperature not more than 270 C and Relative Humidity not more than 45 %.

      Yield:

  1. Theoretical Yield is 3.0 Lac capsules.
  2. Expected Practical Yield is 3.0 Lac ± 2% capsules.

      Packing Details:

  1. Blister Pack the filled and polished capsules by using Triple Track Blister Packing Machine as per its
  2. Put 20 strips each containing 10 capsules in carton.
  3. Seal the unit carton from both ends with cello tape.
  4. Pack the 60 unit cartons in specified corrugated boxes S-11 to give a pack size of 60 x 20 x 10 capsules.
  5. Seal the each corrugated box with adhesive tape and label it properly by affixing the specified label

MANUFACTURING PROCESS:

  1. Fit the mesh # 20 Stainless Steel Sieve on the Sifter as per its SOP  and place Stainless Steel Container below the discharge hopper.
  2. Sift the 0.600 kgs of Aerosil through 20 mesh Stainless Steel Sieve on the sifter and let it to collect in the container kept below the discharge hopper.
  3. Sift the 7.5 kgs of Di-Calcium Phosphate through 20 mesh Stainless Steel Sieve on the sifter and collect in the same container.
  4. Sift the 15.0 kgs of Diclofenac Sodium through 20 mesh Stainless Steel Sieve on the sifter and collect in the same container.
  5. Sift the 2.4 kgs of Magnesium Stearate through 20 mesh Stainless Steel Sieve on the sifter and collect in the same container.
  6. Sift the 4.5 kgs of Talcum through 20 mesh Stainless Steel Sieve on the sifter and collect in the same container.
  7. Sift the 30.0 kgs of Nimesulide through 20 mesh Stainless Steel Sieve on the sifter and collect it in another stainless steel container.
  8. Transfer all the ingredients sifted to Roto Cube Blender. Mix 18 kgs of Calcium Sulphate granules to these ingredients and allow to blend together for 1 hour by operating, Roto cube Blender as per its SOP Weigh the whole batch. The weight of blended powder should be in range of 77.220 kg – 78.00 kg.
  9. Send the sample to Quality Control Department for bulk testing.
  10. Start filling of Empty Hard Gelatin capsules, 260 miligrams of blended powder in each capsule shell by using Automatic Capsule Loading Machine and Semiautomatic Capsule Filling Machine as per their SOP 
  11. Polish the filled capsules by using Feeder, Sorter & Capsule Polishing Machine With A.D.U. as per its SOP 
  12. Blister pack the filled and polished capsules by using Triple Track Blister Packing Machine 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 manufacturing, filling, polishing and packaging of the capsules.
  • Relative Humidity –   Less than 45 %
  • Temperature –   25 0C ± 2 0C
  1. The total weight of blended powder should be checked in the presence of Assistant Manufacturing Chemist and record the same in Batch Manufacturing Record.
  2. Bulk sample should be sent for analysis to Quality Control Department before starting the filling of hard gelatin capsules.
  3. Intermittently the Assistant Manufacturing Chemist should check weight variation of filled capsules at interval of 30 minutes and record for the same should be kept in Batch Manufacturing Record.
  4. Detect out of limit capsules by Weight Variation Method as follows:
  5. a) Take the average weight of 20 Capsules 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 CAPSULES
(in mg)
MAXIMUM PERCENTAGE DIFFERENCE                                                                      ALLOWED
Less than 300 mg 10
300 mg or More 7.5

b) Take the weight of individual Capsules and check if all the Capsules are lying with in the limits.

c) Select the Capsules only if no more than two Capsules are out of percentage limit and if none Capsule differs by more than 2.5 times the percentage limit, otherwise reject the Capsules.

  • Capsules taken for testing and In-process control should not be added to the bulk batch to avoid mix-ups and cross-contamination.
  • Inspection, sorting and polishing of filled capsules should be done as per SOP 
  • Disintegration of filled capsules should be done using Disintegration Testing Apparatus.
  • Disintegration is the time required for the group of capsules to disintegrate. 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 capsules in each of 6 tubes along with a plastic disc over the capsules.
  •  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 t
  • Introduce a tube assembly unit into glass beaker in such a way that wire mesh at the base of each tube is atleast 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 capsules 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 capsules 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 capsules and record the same in Batch Manufacturing Record.
  • Disintegration Time of filled capsules = Not more than 15 minutes
  • The strips and cartons should be checked thoroughly for proper batch coding.
  • 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.
  • 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 Quality Control Analyst has given the ‘Line Clearance’.
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