Master formula Thiamine Mono-Nitrate,Riboflavine and Pyridoxine Hydrochloride Capsules

Master formula Thiamine Mono-Nitrate,Riboflavine and Pyridoxine Hydrochloride 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:

Thiamine Mono-Nitrate,Riboflavine and Pyridoxine Hydrochloride Capsules

BATCH SIZE:  10.0 LACS
PRODUCT REFERENCE CODE: 205 UNIT SIZE:  10 X 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:

 Thiamine Mono-Nitrate         I.P.   10 mg                                    Cynocobalamin                 I.P.       5 mcg

Riboflavine                                I.P.     5 mg                                    Niacinamide                      I.P.      45 mg

 Pyridoxine Hydrochloride     I.P.   1.5 mg                                   Calcium Pantothenate      I.P.        5 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 Blister Packing Machine

Raw materials:

S.NO. INGREDIENTS STD Theoretical Quantity Req. Overages % Total Quantity Used
1. AEROSIL B.P. 0.400 0.400 KGS
2. DI CALCIUM PHOSPHATE I.P. 200.000 200.00 KGS
3. CALCIUM PANTOTHENATE I.P. 5.000 10.00 5.500 KG
4 E.C. NAVY BLUE/ YELLOW (SIZE: 0) (BLUE / YELLOW) 100000.000 100000.000 NOS
5 MAGNESIUM STEARATE I.P. 5.000 5.000 KGS
6 NIACINAMIDE I.P. 45.000 10.00 49.500 KGS
7 SPIRIT CHLOROFORM I.P. 0.450 0.450 Lts
8 STARCH I.P. 237.000 237.000 KGS
9 TALCUM I.P. 5.000 5.000 KGS
10 VITAMIN – B2 (PLAIN) I.P. 5.000 20.00 6.000 KGS
11 VITAMIN – B1

(MONO NITRATE)

(MONO NITRATE)

I.P. 10.000 25.00 12.500 KGS
12 VITAMIN – B6 HCl I.P. 1.500 25.00 1.875 KGS
13 VITAMIN – B12 I.P. 5.000 100.00 10.000 GMS

Packing materials: 

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

RECORD

TOTAL QUANTITY USED
1 220 MM CLEAR (PVC) 180.00 180.00 KG
2 ADHESIVE TAPE ROLL BROWN 2.000 2.000 NOS
3 ALUMINIUM BLISTER FOIL

BEDEX FORTE (3 TRACK)

40.000 40.000 KGS
4 CORRUGATED BOX 92.000 92.000 NOS
5 UNIT CARTON (10 X 30)

BEDEX FORTE

3333.00 2.000 3335.000 NOS
6 CELLO TAPE 10.000 10.000 NOS

MANUFACTURING SPECIFICATION:

  1. Use number zero size Navy Blue-Yellow Capsules.
  2. Moisture content of powder should be less than 2.0 %.
  3. Average fill of each capsule is 500 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 11.9 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%.
  8. Starch contains moisture, therefore during drying of starch in tray drier at 70o C loss on drying should be taken care of.

Yield:

  • Theoretical Yield is 10.0 Lacs capsules.
  • Expected Practical Yield is 10.0 Lacs + 2% capsules.

        Packing Details:

  1. Blister the filled and polished capsules by using Triple Track Blister Packing Machine as per its SOP.
  2. Put 10 strips each containing 30 capsules in carton.
  3. Seal the unit carton from both ends with cello tape.
  4. Pack the 36 unit cartons in specified corrugated box  to give a pack size of 36 x 10 x 30 capsules.
  5. Seal the each corrugated box with adhesive tape and label it properly by affixing the specified label.

MANUFACTURING PROCESS: 

Fit the 40 No. Stainless Steel Sieve on the Sifter as per its SOP and place Stainless Steel Container below the discharge hopper.

Sift the 180 kgs of Di-Calcium Phosphate through #40 mesh Stainless Steel Sieve on the sifter and let it to collect in the container kept below the discharge hopper.

Sift the 0.400 kgs of Aerosil through #40 mesh Stainless Steel Sieve on the sifter and collect in the same container.

Sift the 5.50 kgs of Calcium Pantothenate through #40 mesh Stainless Steel Sieve on the sifter and collect in the same container.

Sift the 5.0 kgs of Magnesium Stearate through #40 mesh Stainless Steel Sieve on the sifter and collect in the same container.

Dry 49.5 kgs of Niacinamide in Tray Drier at 60°C for 45 minutes and sift it through #40 mesh Stainless Steel Sieve on the sifter and collect in the same container.

Sift the 5.0 kgs of Talcum through #40 mesh Stainless Steel Sieve on the sifter and collect in the same container.

Sift the 6.0 kgs of Vitamin B2 plane through #40 mesh Stainless Steel Sieve on the sifter and collect in the same container.

Sift the 12.5 kgs of Vitamin B1 mono through #40 mesh Stainless Steel Sieve on the sifter and collect in the same container.

Sift the 1.875 kgs of Vitamin B6 HCl through #40 mesh Stainless Steel Sieve on the sifter and collect in the same container.

Triturate and dissolve 10 gms of Vitamin B12 in 450 ml of Spirit Chloroform in Stainless Steel Containers.

Sift the 20 kgs of Di-Calcium Phosphate through 40 mesh Stainless Steel Sieve on the sifter and collected in another stainless steel container and perform the following:

To this add the solution of Vitamin B12 prepared in the step no. 11. Mix it thoroughly with Stainless Steel Spatula until uniform.

Dry it in the Tray Drier 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 214.215 kgs of Starch 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 whole batch should be in range of 495.00 kg – 500.00 kg.

Send the sample to Quality Control Department for bulk testing.

Start filling of Empty Hard Gelatin capsules, 500 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 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:

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 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 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:

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’.

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