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

Ingredient Standard Quantity

 Per batch In kg

METFORMIN HYDROCHLORIDE 100.60*
CARMELLOSE SODIUM 10.00
PURIFIED WATER 18.60
HYPROMELLOSE 26.00
CELLULOSE,MICROCRYSTALLINE (DIRECTLY  COMPRESSIBLE,PH 102) 9.5
MAGNESIUM STEARATE 1.5
POVIDONE 1.5
SILICA , COLLOIDAL .ANHYDROUS 1.5

* 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

Stage Equipment

Name

Process Variables Observation

 

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

 

Blade orientation  
Mutlimill  speed  
Screen size of Multimill & Sifter Sifter  
Multimill  
Integrity of screen of Multimill & Sifter   Sifter Multimill
Before    
After    
Sifting Vibrosifter Sieve size  
Integrity of sieves Before  
After  
Sifting time  
Dry mixing RMG

 

Running capacity of RMG (%)  

 

Mixer speed  

 

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

 

Effective kneading time  

 

Binder addition time
Amperage load of mixer  

 

Amperage load of chopper
Drying FBP Inlet air temperature
Outlet air temperature
Bed temperature
% Flap opening
Drying time
LOD of granules (After complete drying)
Milling of Granules Sifter cum multimill

 

 

Blade orientation
Mutlimill  speed
Screen size of Multimill & Sifter Sifter
Multimill
Integrity of screen of Multimill & Sifter Sifter Multimill
Before
After
Sifting of Post Granulation Ingredients Vibro sifter Sieve Size
Integrity of Sieve Before
After
Sifting time
Lubrication

 

Conta Blender Blender 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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About Pharmaceutical Guidanace

Ms. Abha Maurya is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 18 years of rich experience in pharmaceutical field. During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, Nectar life Science Ltd. During his experience, he face may regulatory Audit i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading a regulatory pharmaceutical company as a head Quality. You can join him by Email, Facebook, Google+, Twitter and YouTube

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