Cough Relief tablet
PURPOSE: This Master Formula has been established to highlight the manufacturing procedure in detail, in-process controls and precautions to be observed in the manufacture and packing of this product. This is an important ever- ready document for the manufacture of this product of desired quality and of uniform standards from batch to batch without any difficulty and loss of time and manpower.
SCOPE: This Master Formula document shall serve as a reference document readily available to the personnel, especially new appointees involved in the manufacture of this product.
RESPONSIBILITY AND ACCOUNTABILITY:It shall be the responsibility and accountability of the in-charge of the manufacturing section and the Production Manager to comply with the procedure laid down in this SOP. The Quality Assurance Department shall be responsible and accountable for the distribution of the controlled copies of this SOP to the concerned persons and to ensure compliance of the procedure laid down in this SOP by the concerned persons.
A. stands for Quality Assurance
M.P stands for Good Manufacturing Practices
WHO stands for World Health Organization
ISO stands for International Organization for Standardization.
QC stands for Quality Control Department.
DISTRIBUTION OF COPIES :
Master Copy : Quality Assurance Department
Controlled Copy No.-1 : Manager Quality Control
Controlled Copy No.-2 ; Production Manager
Controlled Copy No.-3 : Manufacturing Section In-charge
MATERIALS AND EQUIPMENTS:
Equipments to be used
|S. No.||Name of Equipment|
|1||Steam Jacketed Starch Paste Preparation Tank|
|2||Sifter Machine –|
|3||Roto Cube Blender|
|4||Rapid Mixer Granulator|
|6||Fluidized Bed Drier|
|8||Sifter Machine – II|
|9||Roto Cube Blender|
|10||Tablet Compression Machine 27 Stations|
|12||Tablet Inspection Machine|
|13||Single Track Blister Packing Machine|
- Raw Materials required for the Standard Batch Size:
|S. No.||Ingredients||Standard||Quantity Required||Overage %age||Total Quantity Required|
|2.||BROMHEXINE HYDROCHLORIDE||B.P||8.000||10.00||8.800 KG|
|4.||DI CALCIUM PHOSPHATE||B.P||55.897||55.897 KG|
|5.||DEXTROMETHORPHAN HBR||B.P||10.000||5.00||10.500 KG|
|9.||MAGNESIUM STEARATE||B.P||10.000||10.000 KG|
|10.||PVPK – 30||B.P||4.716||4.716 KG|
|11||SODIUM BENZOATE||B.P||5.000||5.000 KG|
|16||TARTRAZINE SUPRA||F.C.F||1.000||1.000 KG|
- Packing Materials Required for the Standard Batch Size:
|S. No.||Name of Material||Quantity Required|
|1.||TOREX TABS AL. BLISTER FOIL||30.000 KG|
|2.||104MM CLEAR PVC||150.000 KG|
|3.||TOREX 10 TABS UNIT CARTON||100000.000|
|4||TOREX 10×10 TABS OUTER CARTON||10000.000|
|5||CELLO TAPE ROLL||8.000|
|6||CORRUGATED BOX E-26||197.000|
|7||HANDLE WITH CARE STICKERS||197.000|
Particulars of the product:
Name of the Product: Dextromethorphan HBr,Guaifenesin,Bromhexine HCl and Chlorpheniramine Maleate tablet.
Standard Batch Size: 10.0 LAC
Nature of Packing:
Pack Size (Unit Carton): 1 x 10 TABS
Pack Size (Outer Carton): 10 x 10 TABS
Master Pack (Corrugated Box): 50 x 100 TABS
Labelled Formula :
Each uncoated Tablet contains:
Dextromethorphan HBr. B.P. 10 mg
Guaifenesin B.P. 100 mg
Bromhexine HCl B.P. 8 mg
Chlorpheniramine Maleate B.P. 2 mg
Date of Expiry: 3 years from manufacture
Location of the Manufacture: TABLET SECTION
Preparation of Starch Paste
Preparation of Starch Paste:
Prepare the starch paste in two lots.
Prepare the starch paste in the manner given below using Steam Jacketed Starch Paste Preparation Tank by operating it as per its.
Dissolve 2.5 kgs of Sodium Benzoate in 5 Liters of DM water and stir continuously.
Add 10.0 kgs of Starch in 10Ltrs D.M. water and make slurry stir continuously.
Dissolve 0.5 kgs of Tartrazine Supra in 82 Ltrs of DM water and mix well.
To this add the solution of sodium benzoate and starch slurry with constant stirring to get a uniform paste.
Repeat the same process for the next lot.
Fit the mesh # 20 Stainless Steel Sieve on the Sifter-I as per its SOP. Sift the all ingredients through it and collect separately in Stainless Steel Container.
Blending:Blend the following ingredients using Roto Cube Blender by operating it as per its SOP for 30 minutes and collect in Stainless Steel Container.
308 kgs of Starch
47.0 kgs of Di Calcium Phosphate
86 kgs of MCCP.
30.8 kgs of Lactose
8.80 kgs of Bromohexine HCl
2.2 kgs of C.P.M.
10.5 kgs of Dextromethorphan HBr
100.0 kgs of Guaiphensin
Mix the above blended ingredients with the Starch paste using Rapid Mixer Granulator by operating it as per its SOP . Add starch paste in such a manner by following the procedure given below so as to achieve proper wetting.
- Divide the blended powder in twenty equal parts.
- Divide the prepared starch paste in twenty equal parts.
- Mix the one part of blended powder and starch paste together in Rapid Mixer Granulator. Similarly mix the other parts in same manner.
Pass the wet dough through a Multi Mill by operating it as per its SOP to convert the moist mass into coarse, granular aggregates.
Dry the granules in Fluidized Bed Drier by operating it as per its SOP at temperature 600 – 700 C for 30 minutes. Cool the granules to room temperature.
Fit the mesh # 14 Stainless Steel Sieve on the Sifter-II as per its SOP. Sift all granules through it and collect in Stainless Steel Container. Break the oversized granules left over the mesh in Oscillating Granulator by operating it as per its SOP and resift them.
Check the total weight of dried granules. Determine the loss on drying and percentage yield of dried granules. Divide the granules in two equal lots.
Lubricate one lot of the sifted granules along the following ingredients in a Roto Cube Blender by operating it as per its SOP for 15 minutes and collect in Stainless Steel Container.
- 3.6 kgs of Aerosil
- 5.0 kgs of Magnesium Stearate
- 10.0 kgs of Starch.
- 7.0 kgs of Talcum.
Repeat the same process for next lot with same quantity mentioned above.
Send the granules for bulk testing to Quality Control Department for assay of Active Ingredients.
Shift all the granules for compression to Tablet Compression Machine 27 Stations by operating it as per its SOP and collect the compressed tablets in Stainless Steel Container.
Transfer the all tablets to tablet inspection machine and sort out the defected tablets by operating it as per its SOP No- SOP and collect the selected tablets in Stainless Steel Container.
Shift the inspected tablets to blister section and blister pack them using Single Track Blister Packing Machine by operating it as per its SOP.
Testing of Bulk product :
Request the Q.C. Laboratory to take sample of the bulk product.
Quantity to be given for test & analysis: 10 TABS
Filling, Sealing and Labelling :
Filling, Sealing and Labelling shall be started only if the bulk product has been declared as standard quality by Q.C laboratory.
Check the volume of the finishes product.
Sampling of the finished product :
Request the Q.C. Laboratory to take sample of the finished product for testing and control sample
Quantity to be taken for the test. : 100 TABS
Quantity to be taken for control sample. : 100 TABS
Expected Yield Percentage at Different Stages:
Theoretical Yield : 100%
Expected Practical Yield : 99.8%
Expected Yield %age : 99.8%
Yield of finished product
Theoretical Yield : 100%
Expected practical yield : 99.7%
Expected yield %age : 99.7%
Disposal of finished product
Labelled and packed finished product shall be kept in quarantine store for observation till the receipt of test report from Q.C. Laboratory.
After the receipt of Pass Report from Q.C. Laboratory, the finished product shall be transferred to Finished Goods Store.
In- process controls and precautions to be observed during the manufacture and packing of this product:
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 Assistant Manufacturing Chemist. If any discrepancy is noticed, it should be immediately brought to the notice of Production Pharmacist and QC/QA Manager.
Physical characteristics of Raw material like colour, odour, and consistency are checked before compounding.
Humidity and temperature should be maintained during the compression of thermolabile products.
Sample of dried granules should be sent to Quality Control Department for the determination of Moisture content.
The total weight of blended powder should be checked in the presence of Assistant Manufacturing Chemist and record the same in Batch Manufacturing Record.
Bulk sample should be sent for analysis to Quality Control Department before starting compression of tablets.
Weight Variation: I) Intermittently weight variation of compressed tablets should be checked at 30 minutes interval by the Assistant Manufacturing Chemist and record for the same should be kept in Batch Manufacturing Record.
Out-of-limit tablets should be checked by Weight Variation Method as given below:
Take the average weight of 20 tablets on the calibrated balance and calculate the upper and lower limit as per the table given below in accordance with IP/BP:
|AVERAGE WEIGHT OF TABLETS|
|MAXIMUM PERCENTAGE DIFFERENCE ALLOWED|
|80mg or less||10|
|More than 80mg and less than 250mg||7.5|
|250mg or more||5|
Take the weight of individual tablets and check if all the tablets are lying with in the limits.
Select the tablets only if no more than two tablets are out of percentage limit and if no tablet differs by more than two times the percentage limit, otherwise reject the tablets.
Adjust the desired weight of the tablets in the Compression Machine by moving weight adjustment cam clockwise or anticlockwise accordingly as per the Standard Operating Procedure of Compression Machine.
Re-check the weight of tablets for further adjustment, if any.
Thickness of Tablets:
Thickness of the tablets should be determined by means of the vernier caliper. The thickness of the tablet should be checked whenever weight adjustments are made.
Hardness of the tablets:
The equipment used is the ‘Monsanto’ type hardness tester. Hardness of the compressed tablets should be checked at regular interval to determine the need for pressure adjustments on the tableting machine.
Hardness of tablets varies between: 2-4 Kg/cm2.
‘Roche Friabilator’ is used for measuring the Friability. The instrument is designed to evaluate the ability of the tablet to withstand abrasion in packaging, handling and shipping.
Adjust the instrument to 25 RPM before adding the tablets.
Weigh 20 Tablets on calibrated balance. Transfer the tablets in the plastic chamber. Close the drum tightly.
Switch on the apparatus. Operate the Friabilator for 100 revolutions.
De-dust and reweigh the tablets. Loss in weight indicates the ability of tablets to withstand the wear.
Take 10 tablets to check the friability, when the average weight of tablet is 1g or more than 1g.
Friability Limit = Less than 1.0%
Disintegration is the time required for the group of tablets to disintegrate into the particles. Disintegration Test should be carried out at regular interval of 1 hour by using Disintegration Test Apparatus.
The tube assembly unit is removed from the glass beaker and from each tube the plastic discs are removed.
Place the tablets in each of 6 tubes along with a plastic disc over the tablets.
The glass beaker is filled with water. The water in the beaker is retained at the temperature of 37+1˚C through out the test by suitably setting the thermostat.
Introduce a tube assembly unit into glass beaker in such a way that wire mesh at the base of each tube is atleast 2.5cm below the surface of liquid when the basket is at highest position.
Switch on the apparatus to move the basket assembly containing the tablets up and down through a distance of 5 to 6 cm at a frequency of 28 to 32 cycles per minute. Start the stopwatch.
When the tablets have disintegrated i.e. when no particles remain on the wire mesh at the bottom of tube, stop the stopwatch. Note the time taken for disintegration of the tablets and record the same in Batch Manufacturing Record.
If one or two tablets fail to disintegrate, the test is to be repeated using 12 tablets.
Disintegration Time of uncoated tablets = Not more than 15 minutes
Disintegration Time of coated tablets = Not more than 30 minutes
Tablets taken for testing and In-process control should not be added to the bulk batch to avoid mix-ups and cross-contamination.
Inspection, sorting of rejected tablets should be done as per SOP.
The strips and cartons should be checked thoroughly for proper batch coding.
Manufacturing Chemist and Production Pharmacist should randomly check that the correct no. of strips are being packed in each cartons and also the number of cartons in each shipper is exactly the same as that shown in proof.
Intimation should be sent to Quality Control Department for finished product sampling and testing.
After the completion of labelling and packaging, the coded cartons should be accounted for and rejected printed material should be destroyed in the presence of QC/QA Manager. Fill the destruction sheet and attach the same in the Batch Manufacturing Record.
It will be ensure that filling or packaging equipment has been properly cleaned after the completion of batch.
Filling or packaging of next product should not commence until the Quality Control Analyst has given the ‘Line Clearance’.
Use PVC 92 mm Clear and Aluminium foil for blister packing.
Blister Pack the inspected and De-dusted tablets by using Single Track Blister Packing Machine.
Pack 1 strip containing 10 tablets in inner pouch.
Put 10 strips each containing 10 tablets in each carton.
Seal each carton from both ends with cello tape.
Pack such 50 cartons in specified corrugated box E-26 to give a pack size of 50 x 10 x 10 tablets.
Seal the each corrugated box with adhesive tape and label it properly by affixing the specified label.
CHANGE CONTROL :
No change in this SOP shall be made unless approved by the Approving Authority.
Any change made in this SOP shall not be implemented without prior approval of the Approving Authority.
In case a person intends to get the damaged/defaced controlled copy of this SOP changed, he shall be provided a Certified Photostat Copy of the Master Copy by the Q.A. Department, stamped as “Duplicate
Copy” in green colour as provided under the SOP titled as “Document Control”.
REVISION RECORD :