Manufacturing Procedure and Flow chart of Metformin Hydrochloride Extended – Release Tablets USP 1000 mg

Manufacturing Procedure of Metformin Hydrochloride Extended-Release Tablets USP 1000 mg

 

 

Bill of Material:

Batch Size:- 100000 Tablets

IngredientStandard Quantity

 Per batch In kg

METFORMIN HYDROCHLORIDE100.60*
CARMELLOSE SODIUM10.00
PURIFIED WATER18.60
HYPROMELLOSE26.00
CELLULOSE,MICROCRYSTALLINE (DIRECTLY  COMPRESSIBLE,PH 102)9.5
MAGNESIUM STEARATE1.5
POVIDONE1.5
SILICA , COLLOIDAL .ANHYDROUS1.5

* Given quantity of Metformin Hydrochloride  is based on

Assay             = 100.00 % w/w

L.O.D             = 0.00   % w/w

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  • Manufacturing Procedure :
    • Manufacturing procedure in brief comprise of following steps:
      • Step – I:-  MILLING : Mill Metformin Hydrochloride, Povidone (K-90) using Comminuting mill fitted with 0.5mm screen at midium speed , hammer forward orientation and collect the material in IPCs.
      • Step – II:-SIFTING : Sift Carmellose Sodium (BLANOSE CMC 7 HF PH) Vibro Sifter fitted with sieve of mesh size 40 collect the sifted material in IPCs.
      • Step – III:-DRY MIXING : Perform dry mixing of Metformin Hydrochloride of step-I  & materials of step-II  in RMG.  (Mix for 6 minutes, mixer at slow speed and chopper off).
      • Step – IV:- SAMPLING: Inform to IPQA Department through In-process Analytical Request to collect the sample of blended granules of step – III, IPQA personnel send the sample to Quality Control Department for testing.
      • Step – V:-WET GRANULATION: Granulate the mixed mass of   step III with water, purified and knead the mass for 4-5 minutes, 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 55-60°C till LOD between 1.5- 2.5 % w/w is achieved at 105 °C for 10 minutes
      • Step – VII:- DRY MILLING : Mill the dried granules of step Step – VI through sifter cum multimill using 1.5 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:-BLENDING/ LUBRICATION :
      • Step – IX A :- Sift, Hypromellose , Cellulose ,Microcrystalline (Directly Compressible ,PH 102 ) through Vibro Sifter fitted with  sieve of mesh size 40 collect the sifted material in IPCs.
      • Step – IX B :-Sift  Magnesium Stearate , Povidone,Silica,Colloidal Anhydrous through Vibro Sifter fitted with sieve of mesh size 40 collect the sifted material in IPCs.
      • Step – IX C:- Add the material of  Step – IX A to the Blender’s Bin of Step – VII and blend for 10 minutes at rpm 6. & then add the material of  Step – IX B and again blend it for 5 minutes at 6 rpm.
      • 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 – IX C, 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 – IX C, into tablets of required specification using 37 station double rotary compression machine fitted with standard dies and punches

 

  • COMPRESSED TABLET SPECIFICATIONS
  • Description : White to off white, capsule shaped, and biconvex, uncoated tablet engraved with “DS” on one side and Plain on the other.
  • Average mass    : 1500 mg
  • Uniformity of mass : Individual weight of 20 tablets should not deviate by more than 5.0 % of the Average mass.
  • Thickness                                  : 7.80 ± 0.2 mm
  • Friability                                    : NMT 1.0 %w/w
  • Hardness                                   : 100-250 N

 

  • IPQA CHECKS: Carry out in-process control /check as per SOP.
  • SAMPLING: Inform to IPQA Department through In-process Analytical Request to collect the sample of tablets for analysis as per approved in process specification.    
  • WEIGHING: Collect the Compressed tablets in HDPE containers lined with double poly ethylene bags & weigh and calculate the final yield of Compressed Tablet.            
  • PACKAGING: After getting approval from IPQA Department, pack the approved tablets of step Step – XIII as per approved BPR.

CRITICAL PROCESS VARIABLES

StageEquipment

Name

Process VariablesObservation

 

Milling  of  Metformin Hydrochloride, Povidone (K-90)Comminuting mill

 

Blade orientation 
Mutlimill  speed 
Screen size of Multimill & SifterSifter 
Multimill 
Integrity of screen of Multimill & Sifter SifterMultimill
Before  
After  
SiftingVibrosifterSieve size 
Integrity of sievesBefore 
After 
Sifting time 
Dry mixingRMG

 

Running capacity of RMG (%) 

 

Mixer speed 

 

Mixing time
Wet Granulation RMGRunning capacity of RMG (%)
Mixer speed
Chopper speed 

 

Effective kneading time 

 

Binder addition time
Amperage load of mixer 

 

Amperage load of chopper
DryingFBPInlet air temperature
Outlet air temperature
Bed temperature
% Flap opening
Drying time
LOD of granules (After complete drying)
Milling of GranulesSifter cum multimill

 

 

Blade orientation
Mutlimill  speed
Screen size of Multimill & SifterSifter
Multimill
Integrity of screen of Multimill & SifterSifterMultimill
Before
After
Sifting of Post Granulation IngredientsVibro sifterSieve Size
Integrity of SieveBefore
After
Sifting time
Lubrication

 

Conta BlenderBlender rpm
Blending time
Capacity of Blender Bin
Compression 37 station double rotary compression machine

 

 

Machine Speed (rpm)
Feed frame  rpm
Dies and Punches

 

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