MASTER FORMULA OF DIPHENHYDRAMINE AND AMMONIUM CHLORIDE EXPECTORANT
PURPOSE: This Master Formula 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 SOP. The Production Pharmacist, 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 Pharmacist
- Copy No. 2: Manager Quality Control
- Copy No. 3: Liquid Section
| PRODUCT NAME:DIPHENHYDRAMINE AND AMMONIUM CHLORIDE EXPECTORANT | BATCH SIZE: 1000 LTRS. |
| PRODUCT REFERENCE CODE: | UNIT SIZE: 50 ml |
| GENERIC NAME: N.A. | PACK SIZE: 12 x 12 x 50 ml |
| DOSAGE FORM: SYRUP | STRENGTH: N.A. |
| EXPIRY DATE: AFTER 24 MONTHS FROM THE DATE OF MANUFACTURING | |
COMPOSITION:
Each 5 ml contains:
Diphenhydramine Hydrochloride I.P. 12 mg Sodium Citrate I.P. 40 mg
Ammonium Chloride I.P. 100 mg Menthol I.P. 0.8 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 – III – 1000 Ltrs. | ||
| 4 | Filter Press | ||
| 5 | Storage Tank – I – 1000 Ltrs | ||
| 6 | Linear Bottle Washing Machine | ||
| 7 | Linear 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. | AMMONIUM CHLORIDE | I.P | 27.600 | 10.51 | 30.501 KGS. |
| 2. | ASPARTUM | I.P | 0.270 | 0.270 KGS. | |
| 3. | CITRIC ACID | I.P | 1.200 | 1.200 KGS. | |
| 4. | CHOCOLATE BROWN COLOUR | F.G | 20.000 | 20.000 GMS. | |
| 5. | DIPHENHYDRAMINE HCL | I.P | 2.816 | 6.53 | 3.000 KGS. |
| 6. | HONEY FLAVOUR | F.G | 1.000 | 1.000 LTRS. | |
| 7. | LIQUID GLUCOSE | I.P | 200.000 | 200.000 KGS. | |
| 8. | MENTHOL | I.P | 0.228 | 9.65 | 0.250 KGS. |
| 9. | RASPBERRY FLAVOUR | F.G | 2.000 | 2.000 LTRS. | |
| 10. | SODIUM BENZOATE | I.P | 5.000 | 5.000 KGS. | |
| 11. | SODIUM CITRATE | I.P | 11.406 | 13.98 | 13.001 KGS. |
| 12. | SPIRIT CHLOROFORM | I.P | 4.5 | 4.500 LTRS. | |
| 13. | SUGAR | F.G | 700.000 | 700.000 KGS |
PACKING MATERIALS:-
| S.NO. | NAME OF THE MATERIAL | THEORETICAL QUANTITY REQ. | FOR
RECORD |
TOTAL QUANTITY USED |
| 1. | 100 ML AMBER ROUND BTLS | 10000.000 | 10000.000 NOS | |
| 2. | ADHESIVE TAPE ROLL BROWN | 3.000 | 2.000 NOS | |
| 3 | GUM ACCACIA | 1.000 | 1.000 KGS | |
| 4 | PILFER PROOFS CAPS – 25 MM | 10000.000 | 10000.000 NOS | |
| 5 | UNIT CARTON | 10000.000 | 2.000 | 10002.000 NOS |
| 6 | LABEL | 10104.000 | 3.00 | 10107.000 NOS |
| 7 | SHRINK FILM 240 X 220 MM | 1667.000 | 1667.000 NOS | |
| 8 | CORRUGATED BOX T- 10 | 104.000 | 104.000 NOS |
MANUFACTURING SPECIFICATION:
- Average fill of each Bottle is 100 ml.
- Volume variation limit allowed in each filled Bottle is 100 ml to 101 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-08 to storage tank L-12 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 10000 Bottles.
- Expected Practical Yield is 10000 + 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 amber glass brute 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 as per its SOP.
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 8 shrinked packets in the Corrugated box. Thus each corrugated box contains 6 x 16 x 100 filled and sealed bottles.
Seal each corrugated box with adhesive tape and label it properly by affixing the specified label
MANUFACTURING PROCESS:
Preparation of Sugar Syrup:
Take Purified water 200.0 Ltrs into Stainless Steel Steam Jacketed Sugar Syrup Preparation Tank.
Run the steam into the jacket so as to heat the water.
Add 700 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 200 kgs Liquid Glucose to the Sugar Syrup Storage Tank and stir it vigrously for half an hour to dissolve it in the Sugar Syrup completely.
Transfer the prepared Syrup from Sugar Syrup Storage Tank to Charging Tank L-08 through transfer pump.
Addition of Ingredients into the Charging Tank while stirring continuously:
Dissolve 5.0 kgs of Sodium Benzoate in 20.0 Ltrs of water and add to the bulk batch.
Dissolve 1.2 kgs of Citric Acid in 5.0 Ltrs of Purified water and add to the bulk batch.
Dissolve 0.270 kgs of Aspartum in 2.0 Ltrs of water and add to the bulk.
Dissolve 30.501 kgs of Ammonium Chloride in 100.0 Ltrs of Purified water and add to the bulk batch.
Dissolve 3.0 kgs of Diphenhydramine HCl in 15 Ltrs of Purified water and add to the bulk batch.
Dissolve 13.001 kgs of Sodium Citrate in 60.0 Ltrs of Purified water and add to the bulk batch.
Dissolve 0.250 kgs of Menthol in 4.5 LTRS of Spirit Chloroform and add to the bulk batch.
Dissolve 20.0 gms of Chocolate Brown Colour in 4.0 Ltrs of hot water and add to the bulk batch.
Add 2.0 Ltrs of Raspberry Flavour to the bulk batch.
Add 1.0 Ltrs of Honey Flavour to the bulk batch.
Make up the volume with DM water to 1000 Ltrs and mix until homogeneous.
Check the pH of Solution to be in between 5.0 – 6.0.
Filter the batch through Filter Press 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 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 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.
Intermittently filled volume should be checked at 30 minutes interval by the Assistant Manufacturing Chemist 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 + 2ml
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.
Expectorant 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 ‘Line Clearance’ has been given by the IPQA.