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 |
COMPOSITION:
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. |
CLEANING
AS PER SOP NO. |
| 1 | Sugar Syrup Manufacturing Tank | ||
| 2 | Sugar Storage Tank | ||
| 3 | Charging Tank – V – 3500 Ltrs. | ||
| 4 | Filter Press | ||
| 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 |
RAW MATERIAL:-
| S.NO | INGREDIENTS | STD | Theoretical Quantity Req. | Overages % | Total Quantity Used |
| 1. | BROMHEXINE HCL | B.P. | 1.600 | 10.00 | 1.760 KGS |
| 2. | ASPARTUM | B.P. | 4.000 | 4.000 KGS | |
| 3 | C.P.M | B.P. | 0.800 | 10.00 | 0.880 KGS |
| 4 | BRONOPOL | B.P. | 0.450 | 0.450 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 |
| 7 | GUAIPHENESIN | B.P. | 20.000 | 5.00 | 21.000 KGS |
| 8 | LIQUID GLUCOSE | B.P | 400.00 | 400.00 KGS | |
| 10 | MENTHOL | B.P. | 0.900 | 0.900 KGS
.200 |
|
| 11 | ORANGE FLAVOUR | F.G | 5.000 | 5.000 LTRS | |
| 13 | P.G | B.P | 45.960 | 45.960 KGS | |
| 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 |
PACKING MATERIAL
| S.NO. | NAME OF THE MATERIAL | THEORETICAL QUANTITY REQ. | FOR
RECORD |
TOTAL QUANTITY USED |
| 1. | 100 ML AMBER ROUND BTLS | 20000.000 | 20000.000 NOS | |
| 2. | ADHESIVE TAPE ROLL BROWN | 3.000 | 3.000 NOS | |
| 3 | LABEL | 20278.333 | 3.000 | 20281.333 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 | |
| 8 | INSERT | 20000.00 | 20000.00 NOS. | |
| 9 | SHRINK FILM 220 X 220 MM | 3333.333 | 3333.333 NOS | |
| 10 | MEASURING CUP | 20000.00 | 20000.00 NOS |
MANUFACTURING SPECIFICATION:
- 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.
Yield:
- Theoretical Yield is 20000 Bottles.
- Expected Practical Yield is 20000 +2% Bottles.
Packing Details:
- 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.
MANUFACTURING PROCESS:
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.
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 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’.