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

• 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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