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
- Manufacturing procedure in brief comprise of following steps:
- 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
|
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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 |
|
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Binder addition time | ||||||
Amperage load of mixer |
|
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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 |