|PURPOSE: This Standard Operating Procedure is written for Cloxacillin Sodium to describe the formulae, manufacturing procedure, specifications, packing details of the dosage form.
SCOPE: This procedure is performed and is applied during the manufacturing of the 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 is 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 : β-Lactam Capsule Section
Each Capsule contains:
Cloxacillin Sodium I.P.
Equivalent to Cloxacillin 250 mg
Amoxycillin Trihydrate I.P.
Equivalent to Amoxycillin 250 mg
EQUIPMENT TO BE USED:
|S. NO.||NAME OF EQUIPMENT||ASSEMBLING
AS PER SOP NO.
AS PER SOP NO.
|2||Double Cone Blender (200kgs)|
|3||Semiautomatic Capsule Loading Machine|
|4||Manual Capsule Filling Machine –I|
|5||Manual Capsule Filling Machine – II|
|6||Single Track Blister Machine|
|S.NO.||INGREDIENTS||STD||Theoretical Quantity Req.||Overages %||Total Quantity Used|
|2||AMOXYCILLIN TRIHYDRATE||I.P||28.750||28.750 KGS|
|3||EC DARK BLUE / LIGHT BLUE
|4||MAGNESIUM STEARATE||I.P.||0.675||0.675 KGS|
|6||CLOXACILLIN SODIUM||I.P.||27.250||27.250 KGS|
1.150 g of Amoxycillin Trihydrate is equivalent to 1 g of Amoxycillin.
1.050 g of Cloxacillin Sodium is equivalent to 1 g of Cloxacillin.
|S.NO.||NAME OF THE MATERIAL||THEORETICAL QUANTITY REQ.||FOR
|TOTAL QUANTITY USED|
|1||84 MM CLEAR (PVC)||16.000||16..000 KGS|
|2||ADHESIVE TAPE ROLL BROWN||1.000||1.000 NOS|
|3||ALUMINIUM FOIL||3.500||3.500 KGS|
|4||CELLO TAPE||2.000||2.000 NOS|
|5||UNIT CARTON ( 10 X 10 )||1000.000||2.00||1.000 NOS|
|6||CORRUGATED BOX N – 34||15.0||15.0 NOS|
- Use numbers zero size Dark Blue/ Light Blue Capsules.
- Moisture content of powder should be less than 2.0 %.
- Average fill of each capsule is 575 milligrams.
- Weight Variation Limit for average weight of 20 Capsules is +5 %
- Disintegration time for each Capsule is not more than 15 minutes.
- Average weight of twenty filled capsules is 13.4 grams.
Mix the batch, Fill and Polish the Capsules and also perform the primary packing of Capsules at temperature not more than 250 C and Relative Humidity not more than 35 %.
- Theoretical Yield is 1.0 Lac capsules.
- Expected Practical Yield is 1.0 Lac ± 2% capsules.
- Blister Pack the filled and polished capsules by using Single Track Blister Packing Machine as per its SOP . Put 10 strips each containing 10 capsules in carton.
- Seal the unit carton from both ends with cello tape.
- Pack the 68 unit cartons in specified corrugated box N-34 to give a pack size of 68 x 10 x 10 capsules.
- Seal the each corrugated box with adhesive tape and label it properly by affixing the specified label.
- Fit the mesh # 40 Stainless Steel Sieve on the Sifter as per its SOP . and place Stainless Steel Container below the discharge hopper.
- Sift the 0.150 kgs of Aerosil through 40 mesh Stainless Steel Sieve on the sifter and let it to collect in the container kept below the discharge hopper.
- Sift the 28.750 kgs of Amoxycillin Trihydrate through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
- Sift the 27.250 kgs of Cloxacillin Sodium through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
- Sift the 0.675 kgs of Magnesium Stearate through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
- Sift the 0.675 kgs of Talcum through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
- Shift all the ingredients sifted above to Double Cone Blender and blend together for 1 hour by operating it as
per its SOP.
- Weigh the whole batch. The weight of whole batch should not be out of the limit i.e. – 1%.
- Send the sample to Quality Control Department for bulk testing.
- Start filling of Empty Hard Gelatin capsules, 575 miligrams of blended powder in each capsule shell by using Semiautomatic Capsule Loading Machine, Manual Capsule Filling Machine –I and Manual Capsule Filling Machine-II as per their SOP .
- Blister packs the filled and polished capsules by using Blister Packing Machine as per its SOP.
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 Assistant 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 manufacturing, filling, polishing and packaging of the capsules.
- Relative Humidity – Less than 35 %
- Temperature – 23 0C ± 2 0C
- 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 the filling of hard gelatin capsules.
- 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.
- Detect out of limit capsules by Weight Variation Method as follows:
- 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
|MAXIMUM PERCENTAGE DIFFERENCE ALLOWED|
|Less than 300 mg||10|
|300 mg or More||7.5|
Disintegration Time of filled capsules = Not more than 15 minutes
b) Place the capsules in each of 6 tubes along with a plastic disc over the capsules.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.
9. Capsules taken for testing and In-process control should not be added to the bulk batch to avoid mix-ups and cross-contamination.
10. Inspection, sorting and polishing of filled capsules should be done as per SOP.
11.Disintegration of filled capsules should be done using Disintegration Testing Apparatus.
i) 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.
ii) The tube assembly unit is removed from the glass beaker and from each tube the plastic discs are removed.
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 2.5cm below the surface of liquid when the basket is at highest position.
vi) 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.
vii) 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.
11. The strips and cartons should be checked thoroughly for proper batch coding.
12. 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.
13. Intimation should be sent to Quality Control Department for finished product sampling and testing.
14. 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.
15. It will be ensure that filling or packaging equipment has been properly cleaned after the completion of batch.
16. Filling or packaging of next product should not commence until the Quality Control Analyst has given the ‘Line Clearance’.