master formula records of Dexamethasone Sodium phosphate injection
COMPOSITION : Each ml Contains:
Dexamethasone Sodium phosphate I.P
equivalent to Dexamethsone phosphate I.P. 4 mg/ml
Methyl paraben 1.8 mg
Propyl paraben 0.20 mg
Water for injection q.s.
BATCH SIZE : 100 Litres
SELF LIFE : 2 Years
PACKAGING : 2 ml White Vial
MANUFACTURING FORMULA :
|Sr. No.||Raw Material||Qty Per ml||Overages||Total qty
|01.||Dexamethasone sodium phosphate
as Dexamethasone phosphate
|4 mg||–||4.0mg||400 gm|
|04.||Methyl paraben||1.8 mg||–||1.8mg||180.0gm|
|05.||Propyl paraben||0.2 mg||–||0.2mg||20.0gm|
|06.||Disodium hydrogen phosphate||1.0mg||–||1.0mg||1.00kg|
|07.||Sodium hydrogen phosphate||0.32mg||–||0.32mg||32.0gm|
|08||Water for injection||q.s.||–||q.s.||q.s.|
CALCULATION : Dexamethasone sodium phosphate
— Equivalente to Dexamethasone phosphate 4mg/ml
— For each ml
— _____________ x 4 mg x 100 Litres
— (Assay – Water)
— ( Assay according to Quality Control Report )
EQUIPMENT USED :
PROCESS STEGE EQUIPMENT AND VESSELS
1) DISPENSING (a) Weighing Machine
2) BULK MANUFACTURING (a) 50 Litre S.S.Tank with lid and stirrer.
(b) 100 Litre S.S.Tank with lid and stirrer.
(c) 142 mm/293 mm filter assembly.
3) FILTERATION (a) Bubble point Apparatus
(b) Filtration Assembly – 142 mm /293 mm
(c) 20 litres/50 litres receivingVessels / filling tank
4) FILLING & SEALING (a) Automatic Vial filling and sealing machine
(b) S.S.Container / Tray
5) VIAL WASHING (a) Vial washing machine
(b) S.S.Boxes / Tray
(c) Dry Heat Sterilization (D.H.S.)
6) OPTICAL TESTING (a) Optical testing tables.
7) BATCH PRINTING (a) Batch printing machine
8) LABELLING & PACKING (a) Labelling machine
(c) Strepping machine
GENERAL DISPENSING PROCEDURES :
THE MAIN STEPS IN DISPENSING AREA :
Transaction with Raw Material Store :
Depending upon the production programme and availability of raw materials,bulk requisitions duly authorized
by Production Manager / Mfg . Chemist , must be given to store , 2 hour’s in advance . While receiving the
materials should be checked by concerned Supervisor for the following :-
b) A.R. Number from Q.C.
d) Checking of weight in the weighing room
e) Physical damage if any.
On receiving the raw materials requisition, the materials are dispensed in the following manner.
Materials contained in polythene bags are first depacked into s.s.container and duly labeled . Materials received
in fibre drums and carbous need not be depacked, only external cleaning with a clean dry cloth is sufficient.
The materials are dispensed as per the requisition duly authorized by Production Manager
/ Mfg.Chemist received from the production department. The materials are weighed on electronic balance.
All the materials dispensed are weighed by on Supervisor and counter checked by another Supervisor.
BULK MANUFACTURING :
1) Clean all the equipment /containers required for bulk manufacturing with (teepol/liquid soap) rinse it with tape water and D.M. Water.
2) In the bulk manufacturing area rinsed twice all the above mentioned items with fresh distilled water.
3) Collect 60 litres fresh distilled water in the tank and start nitrogen flushing 30 minutes.
4) Then add disodium E.D.T.A.,sodium metabisulphite with continuous sterring.
5) Collect 10 litres disttiled water for injection heated and boiled then add methyl paraben and propyl paraben.
6) Collect 2 litres water for injection disodium hydrogen phosphate and then sodium dihydrogen phosphate.
7) Solution 3 , 4 ,5,6 & Dexamethasone sodium phosphate with continuous sterring to clear solution .
8) Finaly check and adjust the pH between 7.5 to 8.5
9) Make up the volume upto 100 litres.
PREPARATION OF FILTER ASSEMBLY :
To be done under controlled environment , use 142 mm / 293 mm filter assembly . Before using , dismantle
all parts of the assembly like plates, lower plate, upper plate, clamps, nozzles , distributors, gasket ,
distributing net etc . wash them with teepol , raw water and then washed with hot distilled water cool them for better handling.
Mounting is done as follows:
- Put lower plate on legs.
- Put distributing net on lower plate on that the sieve is kept.
- Put membrane filter on sieve, do not touch the paper on any surface. Put some distilled water on the paper
- so it get soaked. Put the pre filter on it,
- Put the upper plate with gasket properly fitted.
- Clamp the filter assembly. Tighten the opposite clamps at a time to avoid any leakages.
- Fix latex tubing.
- Perform bubble point test at 40 pound pressure. If it passes the bubble point then sterilize it. If it fails then mount the filter paper again . Filter assembly should not be fully airtight while sterilizing.
Sterilization of filter assembly is done at 117 0 C for 30 minutes. After sterilization, filter the prepared batch ,
filtered the solution in sterilized S. S. receiving vessels. Bubble point test perform before and after the filtration.
VIAL WASHING :
- Decarton the vials in clean plastic creates in aseptic area.
- Transfer the creates in washing room.
- Arrange these vials in S.S. trays.
- Load tray in vials washing machine.
- Put on the cycle.
- Vials are washed through unit with 5 micron filtered D.M. water with alternate the flushing with filtered compressed air.
- Unload the machine and arrange.
- The vials into S.S. tray for dry heat sterilizations.
To be sterilized at minimum 200° C for 1 hour.
STERILIZATION OF SOLUTION :
The product is aseptically filled . Sterilization is achieved by filtering through a membrane filter.
Filtration is done through a 142 mm/293 mm membrane filter of 0.22 micron size. Prefilter1.5micron used is 142 mm/293 mm.
- FILLING UNIT :
It consist, of S.S. syringes, holders, filling needles, gassing needles, silicone tubing etc.
The above should be first cleaned carefully with teepol, raw water and then washed with hot distilled water. After cleaning. Syringes deeped in distilled water and kept in S.S. tank which are then invaded into the autoclave for sterilizing. The sterilization cycle is 117°c for 30 minutes.
- RECEIVING VESSELS :
Vessels which are used to collect the filtered solution have to be first washed with teepol solution steamed, then washed with hot distilled water and taken into the unit preparation area. Here they are rinsed twice with fresh distilled water . The opening of vessals are then sterilized at 117 0 C for 30 minutes.
- GARMENTS :
Garments that are used in the sterile filling area are first checked if they are torn . Torn garments are rejected. Clean garments are then folded property and two sets are put into one sterilization box open loaded into the autoclave for sterilization . The sterilization cycle is 117 o C for 30 minutes . After sterilization the perforation are closed . The garments are taken to the air lock and are hanged on to hangers.
- GLOVES :
New gloves are washed thoroughly with DM water and then with distilled water. The gloves are also checked for any tearing and if found any, rejected . These gloves are then put into s.s. unit boxes with the perforation open and sterilized at 1170 C for 30 minutes.
FILING OPERATION :
Filling of vials with sterile solution is done in sterile area. Vials filling is done on one head vial filling and sealing machine.
Filling capacity of the machine is 30 Vials per minute . During filling, the production supervisor has to conduct creation in process control test at regular interval.
In process Test Frequency
a) Fill volume 2.0 to 2.2 ml 30 minutes
b) Nitrogen gassing is proper or not every one hour
c) Sealing quantity every one hour
d) Optical checking every one hour
Write filing is going on movement should be restrained and there should be less talking. The machine should be kept clean.
During lunch break the full area should be cleaned , spraying of antiseptic solution should be taken up at regular intervals.
Sterilization by filteration.
VISUAL INSPECTION :
Sterilized vials are taken for visual inspection .Visual inspection is done on inspection table .The inspection is fitted with a source of illumination such as tube light . The screen has half the area paint-
ed with white and half the area painted in black . The front of the light is covered so that the direct light does not fall on the a separate table . The vials are checked by swirling its contects by wrist movement and observe for any particle or foreign matters . There should be a gap of 5 to 10 minutes after one hour of working. Trained operators should only be allowed.
Type of rejection:
1) Black particles
2) White particles
4) Glass particles
5) Shining matters
6) Sealing rejection
7) Less / high volume
Product Name : Dexamethasone sodium phosphate injection I.P.4mg/ ml vial
Self life : 2 Years
Colour : Clear, colourless solution.
Contents : 2.15 ml
pH : 7.5 to 8.5
Assay : Dexamethsone sodium phosphate I.P.
Equivalent to Dexamethasone phosphate 4mg/ml
Limit 95 % to 105 %
Theoretical yield at different stages :
Scheduled fill : 46511 yield permissible limit
Filling rejection 1.5 % : 697 45814 0 to 2.5%
Optical checking rejection 6% : 2790 43721 0 to 8.0 %
Total rejection : 3487
Normal yield : 43024
After optical inspection vials are kept on labeling machine .
PACKING DETAILS : Box of 25 x 2 ml
Outer of 60 x 25 x 2ml
INPROCESS CONTROLS :
At the start of the batch the printing of the labels should be checked and signed by competent person.
Periodic check has to be done so that the labeled vials have a good aesthetic appearance.
Vial labels are overprinted in label printing machine / by hand stamping with batch no.,Mfg.date, Exp.Date, Retail price and any specific instruction.
Vials are labeled on labeling machine after getting line clearance . The capacity of the machine is 80vials
per minutes. The vials are checked for authentic appearance and any cross labeled / dirty labeled vials are delab-elled
and labeled again . After labeling vials are kept in cartons, inner boxes and then kept in outer boxes. Outer boxes are
passed for taping with printed BOPP tape by taping machine . After packing is over left out labels are counted and destroyed .
FINISHED PRODUCT :
After final packing store in a segregated storage area .Finished products which are “ UNDER TEST ’’ must be quarantined
and segregated by fixed printed labels.