Chlorpheniramine Maleate & Bromhexine hydrochloride Syrup
PURPOSE: This Master Manufacturing formula (MFR) is written to describe the formulae, manufacturing procedure, specifications, packing details of dosage form.
SCOPE: This MFR 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 MFR. The Production Manager, 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 Manager
- Copy No . 2 : Manager Quality Control
- Copy No. 3 : Liquid Section
|PRODUCT NAME: Chlorphenarmine Maleate & Bromhexine hydrochloride Syrup||BATCH SIZE: 2000 LTRS.|
|PRODUCT REFERENCE CODE:||UNIT SIZE: 100 ML|
|GENERIC NAME: N.A||PACK SIZE: 12 x 6 x 100 ml|
|DOSAGE FORM: SYRUP||STRENGTH: N.A.|
|DEPARTMENT: LIQUID DEPARTMENT||EXPIRY DATE: AFTER 36 MONTHS FROM THE DATE OF MANUFACTURING|
Each 5 ml contains:
Chlorpheniramine Maleate B.P. 2 mg Guaiphenesin B.P. 50mg
Bromhexine hydrochloride B.P. 4 mg Dextromethorphan HBr B.P. 5 mg
EQUIPMENTS TO BE USED:
|SR. NO.||NAME OF EQUIPMENT||ASSEMBLING
AS PER SOP NO.
AS PER SOP NO.
|1||Sugar Syrup Manufacturing Tank|
|2||Sugar Storage Tank|
|3||Charging Tank – V – 3500 Ltrs.|
|5||Storage Tank – III – 3500 Ltrs|
|6||Linear Bottle Washing Machine|
|7||Digipack Bottle Filling and Sealing Machine|
|8||Automatic Bottle Labelling Machine|
|9||Shrink Packing Machine|
|S.NO||INGREDIENTS||STD||Theoretical Quantity Req.||Overages %||Total Quantity Used|
|1.||BROMHEXINE HCL||B.P.||1.600||10.00||1.760 KGS|
|5||BRILLIANT BLUE COLOR||F.C.F||20.000||20.000 GMS|
|6||DEXTROMETHORPHAN HBR||B.P.||2.000||5.00||2.100 KGS|
|8||LIQUID GLUCOSE||B.P||400.00||400.00 KGS|
|11||ORANGE FLAVOUR||F.G||5.000||5.000 LTRS|
|14||BENZOIC ACID||B.P.||1.000||1.000 KGS|
|15||SPIRIT CHLOROFORM||B.P.||18.000||18.000 LTRS|
|16||TARTRAZINE SUPRA||FCF||0.100||0.100 GMS|
|17||PHARMA GRADE SUGAR||F.G||1400.00||1400.000 KGS|
|S.NO.||NAME OF THE MATERIAL||THEORETICAL QUANTITY REQ.||FOR
|TOTAL QUANTITY USED|
|1.||100 ML AMBER ROUND BTLS||20000.000||20000.000 NOS|
|2.||ADHESIVE TAPE ROLL BROWN||3.000||3.000 NOS|
|4||UNIT CARTON||20000.000||2.000||20002.000 NOS|
|5||CORRUGATED BOX||278.333||278.333 NOS|
|6||GUM ACCACIA POWDER||1.000||1.000 KGS|
|7||P. P. CAPS 25 MM(NEOMED)||20000.000||20000.000 NOS|
|9||SHRINK FILM 220 X 220 MM||3333.333||3333.333 NOS|
|10||MEASURING CUP||20000.00||20000.00 NOS|
- Average fill of each Bottle is 100 ml.
- Volume variation limit allowed in each filled Bottle is 100 ml to 102 ml.
- Make up the final volume of the syrup accurately.
- Filter the completely charged batch using Filter Press L-21 by operating it as per its SOP.
- Transfer the syrup from charging tank L-10 to storage tank L-14 after complete charging of batch.
- Mix the batch, Fill the bottles and also perform the primary packing of bottles at temperature not more than 250 C and Relative Humidity not more than 40.
- Theoretical Yield is 20000 Bottles.
- Expected Practical Yield is 20000 +2% Bottles.
- Wash the bottles on Linear Bottle Washing Machine L-24 and operate it as per its SOP.
- Transfer the Syrup from storage tank to Digipack Bottle Filling and Sealing Machine L-25 for filling and then Sealing of the bottles as per its SOP.
- Fill 100 ml syrup in White glass round bottle and use 25 mm PP Cap to seal the bottle mouth.
- Inspect the each filled and sealed bottle for proper sealing and presence of the foreign particles, if any.
- Label every inspected bottle by using the Automatic Bottle Labelling Machine L-26.
- Pack each filled and sealed bottle in unit carton individually.
- Make a group of 6 bottles packed in unit cartons.
- Wrap this bundle in the thermoplastic film and shrink pack it by operating Shrink Packing Machine L-27 as per its SOP.
- Pack such 12 shrinked packets in the Corrugated box. Thus each corrugated box contains 6 x 12 x 100 ml filled and sealed bottles. Seal each corrugated box with adhesive tape and label it properly by affixing the specified label.
I) Preparation of Sugar Syrup:
- Take Purified water 450 Ltrs into Stainless Steel Steam Jacketed Sugar Syrup Preparation Tank.
- Run the steam into the jacket so as to heat the water.
- Add 1400 kgs of sugar into the tank and start stirring by operating the tank .
- Heat continuously till the sugar dissolves completely to give uniform Sugar Syrup.
- Transfer the prepared Sugar Syrup to Sugar Syrup Storage Tank through transfer pump.
- Transfer the 400 kgs Liquid Glucose to the Sugar Syrup Storage Tank and stir it vigorously for half an hour to dissolve it in the Sugar Syrup completely.
- Transfer the prepared Syrup from Sugar Syrup Storage Tank to Charging Tank through transfer pump.
II) Addition of Ingredients into the Charging Tank L-10 while stirring continuously:
- Dissolve 1.0 kgs of Benzoic acid in 30 Ltrs of hot Purified water and add to the bulk batch.
- Dissolve 0.880 kgs of C.P.M in 4 Ltrs of Purified water and add to the bulk batch.
- Dissolve 4.00 kgs of Aspartum in 10 Ltrs of Purified water and add to the bulk batch.
- Dissolve 0.450 kgs of Bronopol in 3 Ltrs of water and add add to the bulk batch.
- Dissolve 1.760 kgs of bromhexine HCl and 21.00 kg Guaiphenesin in 45.906 kg of hot P.G and add to the bulk batch.
- Dissolve 2.1 kgs of Dextromethorphan HBr in 15 Ltrs of hot Purified water and add add to the bulk batch
- Dissolve 0.900 kgs of Menthol in 18ltrs of Spirit Chloroform and add to the bulk batch
- Dissolve 0.100 kgs of tartrazine Supra in 3 Ltrs of hot Purified water and add to the bulk batch.
- Dissolve 20 gms of brilliant blue Colour in 1 Ltr of water and add add to the bulk batch.
- Add 8.0 Ltrs of Orange Flavour to the bulk batch.
- Make up the volume with DM water and mix until homogeneous.
- Check the pH of Solution to be in between 5.0 – 5.5.
- Filter the batch through Filter Press L-21 by operating it as per its SOP and transfer it to the Storage Tank.
- Send the sample to Quality Control Department for bulk testing.
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 Manager and QC/QA Manager.
- Physical characteristics of Raw material like colour, odour, and consistency are checked before compounding.
- Final volume should be made as per Standard Operating Procedure using correct dipstick in the Presence of Manufacturing Chemist.
- 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.
- The Manufacturing Chemist should check intermittently filled volume at 30 minutes interval and record for the same should be kept in Batch Manufacturing Record.
- 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 + 2%
- 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.
- Suspensions should be filled under constant slow speed stirring to maintain uniformity of contents.
- The labels and cartons should be checked thoroughly for proper batch coding.
- Intimation should be sent to Quality Control Department for finished product sampling and testing.
- 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.
- It will be ensure that filling or packaging equipment has been properly cleaned.
- Filling or packaging of next product should not commence until the IPQA has given the ‘Line Clearance’.