MFR OF NYSTATIN SUSPENSION

PURPOSE: This Standard Operating Procedure 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 the Manufacturing Chemist to follow and adhere to this SOP. The Production Manager, QC/QA Manager are accountable for the strict adherence to the master

COPY ISSUED TO:

1. Master Copy: Manager Quality Assurance
2. Copy No. 1: Production Manager
3. Copy No. 2: Manager Quality Control
4. Copy No. 3: Liquid Section

PRODUCT NAME: NYSTATIN SUSPENSION	BATCH SIZE:  1000 LTRS.
PRODUCT REFERENCE CODE:	UNIT SIZE:  30 ml
GENERIC NAME: N.A.	PACK SIZE:  12X12X30
DOSAGE FORM: SUSPENSION	STRENGTH: 100000I.U.
DEPARTMENT:  LIQUID DEPARTMENT	EXPIRY DATE: AFTER 24 MONTHS FROM THE DATE OF MANUFACTURING

COMPOSITION: 

Each   ml contains:

Nystatin                  B.P.        100000I.U.

EQUIPMENTS TO BE USED: 

SR. NO.	NAME OF EQUIPMENT	ASSEMBLING AS PER SOP NO.	CLEANING AS PER SOP NO.
1	Charging Tank –III – 1000 Ltrs.
2	Colloidal Mill
3	Storage Tank – I – 1000 Ltrs
4	Linear Bottle Washing Machine
5	Digipack bottle Filling And Sealing Machine
6	Automatic Bottle Labelling Machine
7	Shrink Packing Machine

RAW MATERIAL:-

S.NO.	INGREDIENTS	STD	Theoretical Quantity Req.	Overages %	Total Quantity Used
1.	AEROSIL	B.P.	4.000		4.000 KGS
2.	BANANA FLAVOUR	F.G.	4.000		4.000 LTR
3.	ASPARTUM (P)	B.P.	6.000		6.000 KGS
4.	CMC SODIUM	B.P.	8.000		8.000 KGS
5	NYSTATIN	B.P	21.300	10.00	23.430 KGS
6	M.P.B.S.	B.P.	1.000		1.000 KGS
7	GLYCERINE	B.P.	300.00		300.00 KGS
8	P.P.B.S	B.P.	0.250		0.250 KGS
9	SODIUM CITRATE	B.P.	15.000		15.000 KGS
10	PHARMAGRADE SUGAR	F.G.	700.000		700.000 KGS
11	SORBITOL SOLUTION	B.P.	50.000		50.000 KGS
12	LIQUID GLUCOSE	B.P.	300.000		300.000 KGS

PACKING MATERIAL:- 

S.NO.	NAME OF THE MATERIAL	THEORETICAL QUANTITY REQ.	FOR RECORD	TOTAL QUANTITY USED
1.	32 ML AMBER ROUND BTLS.	33333.00		33333.00 NOS
2.	ADHESIVE TAPE ROLL BROWN	10.000		10.000 NOS
3	UNIT CARTON	33333.000	2.000	33335.000 NOS
4	GUM ACCACIA POWDER	3.000		3.000 KGS
5	PILFER PROOFS  CAPS 25 MM	33333.000		33333.000  NOS
6	CORRUGATED BOX	231.000		231.00 NOS
7	SHRINK FILM 220 X 220 MM	2778.000		2778.000  NOS
8	LABELS	33565.000	3.000	33568.000 NOS

MANUFACTURING SPECIFICATION:

1. Average fill of each Bottle is 30 ml.
2. Volume variation limit allowed in each filled Bottle is 30 ml to 32 ml.
3. Make up the final volume of the suspension accurately.
4. Transfer the suspension from charging tank L-08 to storage tank L-12 after complete charging of batch.
5. Mix the batch, Fill the bottles and also perform the primary packing of bottles at temperature not more than 25˚C.

 Yield:    Theoretical Yield is 33333.333 Bottles.

• Expected Practical Yield is 33333.333 + 2% Bottles.

         Packing Details:

1. Wash the bottles on Linear Bottle Washing Machine L-24and operate it as per its SOP.
2. Transfer the Syrup from storage tank to Linear Bottle Filling and Sealing Machine L-29 for filling and then sealing of the bottles as per its SOP.
3. Fill 30 ml suspension in 32 ml amber glass bottle and use 25 mm PP Cap to seal the bottle mouth.
4. Inspect the each filled and sealed bottle for proper sealing and presence of the foreign particles, if any.
5. Label every inspected bottle by using the Automatic Bottle Labelling Machine L-26 as per its SOP.
6. Pack each filled and sealed bottle in unit carton individually.
7. Make a group of 12 bottles packed in unit cartons.
8. Wrap this bundle in the thermoplastic film and shrink pack it by operating Shrink Packing Machine  as per its SOP.
9. Pack such 18 shrinked packets in the Corrugated box , Thus each corrugated box contains 12X12X30ml filled and sealed bottles.
10. Seal each corrugated box with adhesive tape and label it properly by affixing the specified label.     

MANUFACTURING PROCESS:

  PREPRATION OF SUGAR SYRUP

1. Take Purified water 800.00 ltrs in to Stainless Steel Steam Jacket Sugar Syrup Preparation Tank.
2. Run the steam in to jacket so as to heat the water
3. Add 700kgs of sugar into the tank and start stirring by operating the tank
4. Heat continuously till the sugar dissolves completely to give uniform Sugar Syrup
5. Transfer the Sugar Syrup to Sugar Syrup Storage Tank.
6. Transfer the 300kgs Liquid Glucose to the Sugar Syrup Storage Tank and Stir it to dissolve completely
7. Soak 8.0kgs of CMC Sodium in 80lltr of Purified Water for 6 hours.

      Addition of Ingredients into the Charging Tank  while stirring continuously:       

1. Dissolve1.000 kgs of MPBS and 0.250kgs of PPBS in 2.5 Ltrs of Purified water and add to the bulk batch.
2. Dissolve 6.000 kgs of Aspartum powder in 15 litres of preheated Purified Water and add to the bulk batch.
3. Dissolve 15.000 kgs of Sodium Citrate in 80 Ltrs of Purified water and add to the bulk batch.
4. Add 4.00 kgs of Aerosil to the bulk batch.
5. Add previously soaked Carboxy Methyl Cellulose Sodium to the bulk.
6. Add 50.00kgs of Sorbitol to the bulk batch.

Now perform the following Take 300kgs of Glycerine in S.S. Charging Tank and add 23.430kgs of Nystatin stir it to dissolve completely and add to the Bulk Batch.

7. Colloid the batch through Colloid Mill by operating it as per its SOP and transfer it to the Tank.
8. Add 4.000 Ltrs of Banana flavours to the Bulk Batch.
9. Make up the volume with Purified water to 1000 Ltrs and mix for 20 minutes.
10. Leave the Suspension to settle for overnight or for minimum 8 hours.
11. Again check the volume and makeup with Purified water to 100 Ltrs and mix for 10 minutes.
12. Check the pH of Solution to be in between 4.5 – 7.5.

13. Send the sample to Quality Control Department for bulk testing. Filter the whole batch through Mesh No. 80.

IN-PROCESS CONTROLS:

The following in-process controls should be maintained during the processing:

1. Check Raw materials used for manufacturing purpose are all approved materials and have ‘Released’ labels fixed on it.
2. 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 Manager and QC/QA Manager.
3. Physical characteristics of Raw material like colour, odour, and consistency are checked before compounding.
4. The final volume should be made as per Standard Operating Procedure using correct dipstick in the Manufacturing Chemist.
5. pH of the bulk should be checked and it should be with in specified limits.
6. Bulk sample should be sent for analysis to Quality Control Department before starting the filling and sealing stage.
7. The  Manufacturing Chemist should check intermittently filled volume at 30 minutes interval and record for the same should be kept in Batch Manufacturing Record.
8. The net volume should be checked for all the filling nozzles and in no case, net volume should be less than volume claimed on the label.

                           Limit for Volume Variation:  Volume claimed on the label + 2ml

9. Visual inspection of filled and sealed bottles should be done as per SOP and the record of the same should be kept in the Batch Manufacturing Record.
10. Suspensions should be filled under constant slow speed stirring to maintain uniformity of contents.
11. The labels and cartons should be checked thoroughly for proper batch coding.
12. Intimation should be sent to Quality Control Department for finished product sampling and testing.
13. After the completion of labelling and packaging, the coded labels and 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.
14. It will be ensure that filling or packaging equipment has been properly cleaned.
15. Filling or packaging of next product should not commence until the Q.A. Analyst has given the ‘Line Clearance’.

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