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:

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
   

   

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: 

RAW MATERIAL:-

PACKING MATERIAL 

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’.

iamraj