Flow Chart and Manufacturing Procedure of Nimesulide Tablets
Bill of Materials
|Ingredient||Pharmacopoeial Status||Pharmaceutical role|
|Silica, Colloidal Anhydrous||Ph.Eur.||Glidant|
|Hydrochloric Acid,Concentrated||Ph.Eur.||pH Adjusting agent|
|Water, purified||Ph.Eur||Vehicle for binder|
List of Process Equipment’s
|2.||Stationary Hydraulic Lift||150 kg/cycle|
|4.||S.S Jacketed kettle||100Ltrs/ cycle.|
|6.||Sifter cum MultiMill||100-250 Kg/cycle|
|7.||FBD Bowl Tipper||250kg/ cycle|
|9.||Conta Blender||600-1200 Ltrs|
|10.||Compression Machine 61 station.||120,200-300,000/Hr.|
|11.||Blister Packing Machine 250 PDA||Max 250 Strips/Min|
|12.||HSAjet TCU Printer||online|
|13.||BOPP Tapping Machine||online|
Equipment’s / Instruments used for In-process checks
The following calibrated equipment’s / Instruments are used for in-process checks.
|S. No.||Equipment /Instrument Name|
|1.||Analytical weighing Balance|
|2.||Halogen Moisture Analyser|
|3.||Friability Test Apparatus|
|6.||Disintegration Test Apparatus|
Manufacturing procedure in brief comprise of following steps:
Step – I : SIFTING : Sift Silica, Colloidal Anhydrous, Maize Starch, Croscarmellose Sodium, through Vibro Sifter fitted with sieve of mesh size 60 collect the sifted material in IPCs.
Step – I : SIFTING : Sift Nimesulide, Lactose Monohydrate through Vibro Sifter fitted with sieve of mesh size 20 collect the sifted material in IPCs.
Step – III : DRY MIXING : Perform dry mixing of sifted materials of step I & II in RMG.(mix for 10 minutes, mixer at slow speed and chopper off ).
Step – IV : BINDER PREPARATION:
Step – IVa:Take S.S containers, add Hydrochloric Acid in Water, Purified & measure pH (by calibrated pH meter ) . pH should be between 2.5-3.5.
Step – IVb: In S.S jacketed kettle (80 to 90 °C) dissolve Docusate Sodium, Povidone (K-30) and Polysorbate 80 in hot Water, purified with continues stirring to obtain a clear solution.
Step – IV c: Add bulk of Step – IVb [temperature of bulk should be between (50 to 60 °C )] to Step – IVa and mix.
Step – V : WET GRANULATION : Add binder solution of Step – IVc to the dry mix Step – III , slowly and mix at mixer slow speed for 3 minutes and knead the mass for 2-4 minutes at mixer fast speed . Add more Water, Purified, if required to achieve the granulation end point.
Step – VI: DRYING : Dry the wet mass of step V in Fluidized Bed Processor at an inlet air Temp. of 75±5°C till LOD in the range of 1.0- 3.0 % w/w is achieved.
Step –VII: DRY MILLING: Mill the dried granules of Step – VI through sifter cum multimill using 2.0 mm screen for sifter and 2.0 mm screen for miller with knives forward orientation at slow speed , collect the granules in Blender’s Bin.
Step –VIII: WEIGHING OF GRANULES :Weighing of granules is done by using a calibrated balance and calculate the actual yield..
Step –IX: SIFTING OF POST GRANULATION INGREDIENTS:
Sift Magnesium Stearate, Silica, Colloidal Anhydrous, Croscarmellose Sodium through Vibro Sifter fitted with sieve of mesh size 40.
Step –X: BLENDING/ LUBRICATION : Add the lubricants of Step –IX to Blender’s Bin of Step –VII and mix for 10 minutes at rpm 8.
Step –XI: WEIGHING :Weighing of lubricated granules is done by using a calibrated balance and calculate the actual yield..
Step –XII: SAMPLING : Inform to IPQA Department through In-process Analytical Request to collect the sample of blended granules of Step –X, IPQA personnel send the sample to Quality Control Department for testing as per In-process Specification.
Step –XIII: COMPRESSION : After getting approval from IPQA Department, compress the lubricated blend of Step –X ,into tablets of required specification using 61 station compression machine fitted with dies and 9.5 mm round, Biconcave Punches,. Dedust the tablet by using tablet dedusting machine.
COMPRESSED TABLET SPECIFICATIONS
Description : Pale yellow coloured, Round, Biconvex, uncoated tablets.
Average Weight : 350 mg
Thickness : 4.6 ± 0.20 mm
Diameter : 9.6 ± 0.05 mm
Hardness : 50 – 100 N
Friability : NMT 1.0 %w/w
Disintegration Time : NMT 15 minutes
Uniformity of Weight : Individual weight of 20 tablets should not deviate by more than 5 % of the average weight.
Step –XIV: IPQA CHECKS : Carry out in-process control /check as per SOP.
Step –XV: SAMPLING : Inform to IPQA Department through In-process Analytical Request to collect the sample of tablets for analysis as per approved in process specification.
Step –XVI: WEIGHING : Collect the Compressed tablets in HDPE containers lined with double poly ethylene bags & weigh and calculate the final yield of Compressed Tablet.
Step –XVII: PACKAGING : After getting approval from IPQA Department, pack the approved tablets of Step –XIII as per approved BPR.