MFR OF CLOTRIMAZOLE & METRONIDAZOLE CREAM
PURPOSE: This Master Formula 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 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:
- Master Copy: Manager Quality Assurance
- Copy No. 1: Production Pharmacist
- Copy No. 2: Manager Quality Control
- Copy No. 3: Ointment Section
| PRODUCT NAME: | CLOTRIMAZOLE & METRONIDAZOLE CREAM | BATCH SIZE: | 500 Kg |
| DOSAGE FORM: | OINTMENT | UNIT SIZE: | 45g |
| EXPIRY DATE: | AFTER 36 MONTHS FROM THE DATE OF MANUFACTURING | PACK SIZE: | 100 ´ 45g |
| COMPOSITION: | ||
| Clotrimazole | B. P. | 2% w/w |
| Metronidazole | B.P | 10% w/w |
| EQUIPMENTS TO BE USED: | |||
| SR. NO. | NAME OF EQUIPMENT | ASSEMBLING
AS PER SOP NO. |
CLEANING
AS PER SOP NO. |
| 1 | Wax Vessel | ||
| 2 | Water Vessel | ||
| 3 | Mixing Vessel | ||
| 4 | Colloidal Mill | ||
| 5 | Storage Container-I (1000 Kg) | ||
| 6 | Semiautomatic Tube Filling & Crimping Machine | ||
| RAW MATERIALS:- | |||||
| 1. | CETO MACROGOL- 1000 | B.P. | 16.500 | 16.500 KG | |
| 2. | CETOCETYL ALCOHOL | B.P. | 50.000 KG | 50.000 KG | |
| 3. | CLOTRIMAZOLE | B.P. | 10.000 KG | 5.00 | 10.500 KG |
| 4. | LIQUID PARAFFIN LIGHT | B.P. | 30.500 KG | 30.500 KG | |
| 5 | METHYL PARABEN (plain) | B.P. | 1.000 KG | 1.000 KG | |
| 6 | PROPYL PARABEN (plain) | B.P. | 0.550 KG | 0.550 KG | |
| 7 | SODIUM METABISULPHITE | B.P. | 1.500 KG | 1.500 KG | |
| 8 | WHITE PETROLEUM JELLY | B.P. | 80.000 KG | 80.000 KG | |
| 9. | METRONIDAZOLE | B.P. | 52.500 KG | 52.500 KG | |
| 10. | P.G | B.P. | 5.000 KG | 5.000 KG | |
| PACKING MATERIALS:- | ||||
| S.NO. | NAME OF THE MATERIAL | THEORETICAL QUANTITY REQ. | FOR
RECORD |
TOTAL QUANTITY USED |
| 1. | ADHESIVE TAPE ROLL | 5.000 | 5.000 NOS | |
| 2. | CELLO TAPE | 5.000 | 5.000 NOS | |
| 3. | TUBES – 45 G | 11111.000 | 11111.000 NOS | |
| 4. | UNIT CARTON | 11111.000 | 3.000 | 11114.000 NOS |
| 5 | INSERT | 11111.000 | 11111.000 NOS | |
| 6 | CORRUGATED BOXES | 110.00 | 110.000 NOS | |
MANUFACTURING SPECIFICATION:
- Average fill of each Tube is 45 grams.
- Weight variation limit allowed in each filled Tube is + 200 mg.
- Melt the ointment base at the maintained temperature 70˚C.
- Use accurate weighed quantity of water to make up the final weight of cream.
- Colloid the cream till uniform particle size is achieved.
- The temperature of primary area should not be more than 30˚C.
Yield:
- Theoretical Yield is 11111 Tubes.
- Expected Practical Yield is 11111 + 2% Tube.
Packing Details:
- Transfer the cream from storage tank to Aluminium Tube Filling & Crimping Machine and start filling and then Crimping of the tubes as per its SOP.
- Pack the filled tubes in unit carton.
- Pack such 12 tubes in each outer carton.
- Seal the outer carton with cello tape.
- Pack the 24 outer cartons in specified corrugated box to give a pack size of 24 x 12 x 45g tubes.
- Seal the each corrugated box with adhesive tape and label it properly by affixing the specified label.
MANUFACTURING PROCESS:
- Melt 16.500 kg of Ceto Macrogol- 1000, 50 kg of Cetocetyl Alcohol, 30.50 kg of Liquid Paraffin Light, 80 kg of White Petroleum Jelly in a Steam Heat Wax Melting Vessel by operating it as per its SOP at 70°
- Heat 321.0kg of water at 70° C in Water Vessel by operating it as per its SOP. Filter and transfer the melted base through Stainless Steel Sieve no. 100 to the Mixing Vessel and start the machine as per its SOP.
- Dissolve 1.000 kg of Methyl Paraben (plain) in 2.0kg of hot water and transfer it to the bulk batch.
- Dissolve 0.550 kg of Propyl Paraben (plain) in 4.0kg of hot water and transfer it to the bulk batch.
- Dissolve 1.500 kg of Sodium Metabisulphite in 6.0kg of hot water and transfer it to the bulk batch.
- Take 30 kg of hot water and suspend 5.25 kg of Clotrimazole and pass it through Colloid Mill to achieve the slurry of uniform particle size by operating it as per its SOP and transfer it to the bulk batch.
- Take 30 kg of hot water and suspend 52.50 kg of Metronidazole and pass it through Colloid Mill to achieve the slurry of uniform particle size by operating it as per its SOP and transfer it to the bulk batch.
- Slowly add rest of water to the bulk batch.
- Cool the cream to the room temperature by running the water in the jacket of mixing vessel.
- Mix the whole batch for 90 minutes while running the water in the jacket.
- Send the sample to Quality Control Department for bulk testing.
- After approval from Quality Control Department, transfer the cream to storage tank.
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.
- The total weight of bulk ointment / cream should be checked in the presence of Manufacturing Chemist and record the same in Batch Manufacturing Record.
- pH of the bulk should be checked and it should be with in specified limits.
- Bulk sample should be sent for analysis to Quality Control Department before starting the filling and sealing stage.
- While the tube filling operation is on, the Manufacturing Chemist should check weight of net filled quantity per tube at the interval of 30 minutes by checking the tare weight of empty tube and gross weight of the filled tube. Record for the same should be kept in Batch Manufacturing Record.
- The ‘fill weight’ of ointment or cream per tube should not be less than the labelled amount.
Limit for Weight Variation: Weight claimed on the carton + 200 mg
- Manufacturing Chemist will also ensure that the crimping of the filled Aluminium tubes, sealing of plastic tubes is appropriate and embossing of batch number and manufacturing date is conspicuous. Also the quality of embossing will be controlled by adjusting pressure exerted by the jaws, so that pinholes are not developed on the embossed letters / numbers.
- The inner and outer cartons should be checked thoroughly for proper batch coding.
- Manufacturing Chemist and Production Pharmacist should randomly check that the correct no. of inner cartons are being packed in each outer cartons and also the correct number of outer 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 filling and packaging, the coded cartons should be accounted for and rejected printed material should be destroyed in the presence of QC/QA Manager. Maintain the destruction of the same in the Batch Manufacturing Record.
- It will be ensure that filling or packaging equipment has been properly cleaned.
- Filling or packaging of next product should be commenced only after getting the ‘Line Clearance’ of the previous product, from the IPQA.