Master formula of Iron, Folic Acid, Vitamin B12 and Calcium Carbonate Capsules
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:
1. Master Copy: Manager Quality Assurance
2. Copy No. 1: Production Pharmacist
3. Copy No. 2: Manager Quality Control
| PRODUCT NAME: Iron, Folic Acid, Vitamin B12 and Calcium Carbonate Capsules | BATCH SIZE: 1.0 LAC |
| PRODUCT REFERENCE CODE: | UNIT SIZE: 10 ´ 30 |
| GENERIC NAME: N.A. | PACK SIZE: 36 ´ 10 ´ 30 |
| DOSAGE FORM: CAPSULE | STRENGTH: N.A. |
| DEPARTMENT: NON β-LACTAM DEPARTMENT | EXPIRY DATE: AFTER 18 MONTHS FROM THE DATE OF MANUFACTURING |
COMPOSITION:
Each Capsule contains:
Ferrous Fumerate I.P. 300 mg
Folic Acid I.P. 1.5 mg
Vitamin B12 I.P. 10 mcg
Calcium Carbonate I.P. 200 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 | A.D.U. | ||
| 8 | Triple Track Blister Packing Machine |
Raw materials:
| S.NO. | INGREDIENTS | STD | Theoretical Quantity Req. | Overages % | Total Quantity Used |
| 1. | AEROSIL | B.P. | 0.080 | 0.080KGS | |
| 2 | CALCIUM CARBONATE | I.P. | 20.000 | 10.00 | 22.000 KGS |
| 3 | EMPTY CAPSULES GREEN / GREEN (0) | – | 100000.000 | 100000.000 NOS | |
| 4 | FOLIC ACID | I.P. | 0.150 | 50.00 | 0.225 KGS |
| 5 | FERROUS FUMERATE | I.P. | 30.000 | 5.00 | 31.500 KGS |
| 6 | MAGNESIUM STEARATE | I.P. | 0.600 | 0.600 KGS | |
| 7 | SPIRIT CHLOROFORM | I.P. | 0.450 ML | 0.450 ML | |
| 8 | STARCH | I.P. | 4.000 | 4.000 KGS | |
| 9 | TALCUM | I.P. | 1.600 | 1.600 KGS | |
| 10 | VITAMIN B – 12 | I.P. | 1.000 | 100.00 | 2.000 GMS |
Packing materials:
| S.NO. | NAME OF THE MATERIAL | THEORETICAL QUANTITY REQ. | FOR RECORD | TOTAL QUANTITY USED |
| 1 | 220 MM DARK GREEN (PVC) | 18.000 | 18.000 KGS | |
| 2 | ADHESIVE TAPE ROLL BROWN | 1.000 | 1.000 NOS | |
| 3 | CORRUGATED BOXEX | 9.259 | 9.259 NOS | |
| 4 | ALUMINIUM FOIL (3 TRACK) | 4.000 | 4.000 KGS | |
| 5 | CELLO TAPE | 1.000 | 1.000 NOS | |
| 6 | UNIT CARTON (10 X 30) | 333.333 | 2.000 | 335.333 NOS |
MANUFACTURING SPECIFICATION:
- Use number zero size Green-Green Capsules.
- Moisture content of powder should be less than 2.0 %.
- Average fill of each capsule is 600 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 13.9 grams.
- 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:
- Theoretical Yield is 1.0 Lac capsules.
- Expected Practical Yield is 1.0 Lac ± 2% capsules.
Packing Details:
- Blister Pack the filled and polished capsules by using Triple Track Blister Packing Machine as per its SOP.
- Put 10 strips each containing 30 capsules in carton.
- Seal the unit carton from both ends with cello tape.
- Pack the 36 unit cartons in specified corrugated box to give a pack size of 36 x 10 x 30 capsules.
- Seal the each corrugated box with adhesive tape and label it properly by affixing the specified label.
MANUFACTURING PROCESS:
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 0.080 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 22 kgs of Calcium Carbonate through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
Sift the 0.225 kgs of Folic Acid through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
Sift the 31.5 kgs of Ferrous Fumerate through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
Sift the 0.600 kgs of Magnesium Stearate through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
Triturate and dissolve 2.0 Gms of Vitamin B12 in 450 ml of Spirit Chloroform in a stainless steel container.
Sift the 1.600 kgs of Talcum through 40 mesh Stainless Steel Sieve on the sifter and collect it in another stainless steel container.
To this add solution of vitamin B12 prepared in step no. 7 and mix it thoroughly with stainless steel spatula until uniform.
Dry it in the tray dryer at 60° C for 30 minutes.
Sieve it through 40 mesh and add to the Roto Cube Blender.
Transfer all the sifted ingredients to Roto Cube Blender. Mix 4.000 kgs of Calcium Sulphate granules to these ingredients and allow blending 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 59.41 kg – 60.0 kg.
Send the sample to Quality Control Department for bulk testing.
Start filling of Empty Hard Gelatin capsules, 600 milligrams of blended powder in each capsule shell by using Automatic Capsule Loading Machine and Semiautomatic Capsule Filling Machine as per their SOP.
Polish the filled capsules by using Feeder, Sorter & Capsule Polishing Machine with A.D.U. as per its SOP.
Blister pack the filled 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:
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 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 45 %
- Temperature – 25 0C ± 2 0C
The total weight of blended powder should be checked in the presence of 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 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:
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 |
Take the weight of individual Capsules and check if all the Capsules are lying with in the limits.
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 thermostat.
Introduce a tube assembly unit into glass beaker in such a way that wire mesh at the base of each tube is at least 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.
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 IPQA has given the ‘Line Clearance’.