MASTER FORMULA RECORD
Product Name: CADPRIL-5 mg TABLETS
Generic Name: Ramipril IP 5mg
1.0 PRODUCT
DETAILS:
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Shelf life: |
Batch Size: |
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Brand Name of Product: | Category: |
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Generic Name of Product: Ramipril Tablet |
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Label Claim |
Each uncoated
tablet contains
;
Excipients……………………….q.s. Colour : |
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Market |
Domestic/Export/ Institutional Supply |
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Marketed By |
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Dosage Form |
Oral dosage form - Tablets |
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Description |
Light brick red
colored capsule shape tablet having break line on one side and plain on
other. |
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Length & Width |
13.20X 5.20 ± 0.2 |
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Average weight of tablets |
Uncoated
tablets: |
250
mg |
Coated Tablets: |
NA |
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Mfg.
Lic. No.: |
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2.0 TABLE
OF CONTENT:
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Sr.
No. |
Partuclars |
Page
No. |
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1. |
Product
Details |
2 |
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2. |
Table
of Content |
3 |
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3. |
Flow-chart
for formulation |
4 |
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4. |
Bill
of raw Material |
5-7 |
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5. |
List
of equipment |
8 |
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6. |
Manufacturing
Process |
8-13 |
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7. |
Batch
Reconciliation |
14 |
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8. |
Revision
history |
14 |
3.0 FLOW-CHART
FOR FORMULATION
Inspection Transfer to packing Un-lubricated granules Drying of FBD NMT 2.0% LOD Wet Granulation in RMG Binder Preparation Dry Mixing in RMG DISPENSING Sifting of all Materials in
vibro sifter PVPK-30,
Starch, Methyl
Paraben, Propyl
Paraben Milling
the wet granules in multi mill through 8.0mm Starch Aerosil (Colloidal Silicon
Dioxide), Lactose, Di Basic Calcium Phosphate Sizing & Milling of dried
granules through Multimill by using 1.5 mm
screen 40# sieve 80# Ramipril, Sodium Starch
Glycolate, Aerosil (Colloidal Silicon
Dioxide), Talc, Cross Povidone, 60#
Magnesium stearate Blending & Lubrication in
blender Compression
4.0 BILL
OF MATERIAL (For 3,00,000 Tabs)
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Sr.
No. |
Ingredients |
Specification |
Quantity Mg Per
Tablet |
Overages % |
Batch
Quantity In Kg (3.0 Lac) |
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Raw
Material for Dry Mixing |
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1.
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Di Basic Calcium Phosphate |
IP |
77.5 |
-- |
23.250 |
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2.
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Starch |
IP |
87.5 |
-- |
26.250 |
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3.
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Lactose* |
IP |
50 |
-- |
15.000 |
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4.
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Aerosil (COLLAIDOL SILICON
DIOXIDE) |
IP |
1.25 |
-- |
0.750 |
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Total Weight |
216.25 |
64.875 |
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Raw
Material for Binding |
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5.
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PVPK-30 |
IP |
4.5 |
-- |
1.350 |
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6.
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Starch for paste |
IP |
8.75 |
-- |
2.625 |
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7.
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Propyl Paraben |
IP |
0.1 |
-- |
0.030
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8.
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Methyl Paraben |
IP |
0.2 |
-- |
0.060 |
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Total Weight |
13.55 |
4.065 |
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Raw
Material for Blending & Lubrication |
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9.
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Ramipril |
IP |
5.00 |
7.00* |
1.605 |
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10. |
Sodium Starch Glycolate |
IP |
5 |
-- |
1.500 |
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11. |
Magnesium Stearate |
IP |
2.5 |
-- |
0.750 |
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12. |
Cross Povidone XL-10 USP28/NF23 |
IP |
7.5 |
-- |
2.250 |
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13. |
Talc for Lubrication |
IP |
5 |
-- |
1.500 |
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14. |
Colour red oxide iron |
IP |
0.625 |
-- |
0.187 |
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Total Weight |
250 |
77.107 |
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*Lactose use LOD compensates
10% during Drying.
Actual Quantity of
RAMIPRIL is to be taken as per the formula given
A. Calculation
for single AR No.:
AR.
No.________________, Assay on dried basis: __________, LOD: ________
Standard QTY.X 100 X 100
Quantity
of Ramipril to be dispensed =----------------------------------------------
= -------------------------------------
=
Assay on as dried basis X (100-LOD)
B. Calculation
for Multiple AR No.:
1st
AR No.: AR. No.________________, Assay on dried basis: __________ , LOD:
________
Q1 (Available
Quantity) X
Assay on as dried basis X (100-LOD)
A1
= ----------------------------------------------
----------------------------------- =
----------------------------------------- =
100 X 100
2nd AR No.:
AR. No.________________, Assay
on dried basis: __________ , LOD: ________
Q2 (Available
Quantity) X Assay
on as dried basis X (100-LOD)
A2
= ----------------------------------------------
----------------------------------- =
----------------------------------------- =
100 X 100
Final
AR No.: AR. No.________________, Assay on dried basis: __________ , LOD:
________
Q3 (Std Qty-A1-A2) X 100 X100
A3
= ---------------------------------------------- ----------------- = ----------------------------------------- =
Assay on as dried basis X (100-LOD)
Total
Qty of API to be dispensed (A4) = A3+Q2+Q1) = ______________
Quantity of Starch is to be adjusted based on quantities of the above Active.
Quantity of Starch in kg = Standard Qty
of Starch – (A4 - Slandered Qty of API) =
5.0
LIST OF EQUIPMENT
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S.
No. |
Name of Equipment |
Equipment ID No. |
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1.
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Vibro Sifter |
PR/TAB/EQ/002 |
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2.
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Rapid mixer granulator (RMG) |
PR/TAB/EQ/001 |
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3.
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Paste kettle |
PR/TAB/EQ/005 |
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4.
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Fluid bed dryer
(FBD) |
PR/TAB/EQ/011 |
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5.
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FBD Bag |
PR/TAB/EQ/005 |
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6.
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Multi-mill |
PR/TAB/EQ/009 |
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7.
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Octagonal blender |
PR/TAB/EQ/004 |
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8.
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Weighing
Balance 300
KG |
PR/TAB/IN/002 |
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9.
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SS scoop |
PR/TAB/EQ/008 |
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10.
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Compression
Machine (Forced Feeder
machine) |
PR/TAB/EQ/006 |
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11.
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Disintegration
Tester |
PR/TAB/DT/001 |
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12.
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Friability
Apparatus |
PR/TAB/FA/001 |
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13.
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Vernier caliper |
PR/TAB/VC/001 |
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14.
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Hardness Tester |
PR/TAB/HT/001 |
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15.
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Weighing Balance
300 gm |
PR/TAB/IN/001 |
6.0
MANUFACTURING PROCESS:
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Step. No. |
Manufacturing
Instruction |
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6.1
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Binder preparation |
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Stap-1 Take purified water in 10 Kg
in paste kettle and Heat up to 90°C now add PVPK 30 (1.350 Kg). and add
methyl Paraben (0.060 kg), Propyl Paraben(0.030 kg) Stap-2 Take Purified water 5.0 Kg in
SS container and add starch 2.625 kg with stirring for 5 minutes. Stap-3 Then Mixing Step-2 in Step-1 |
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6.2
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Dry Mixing |
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Take
sifted material for dry mixing and mix all the material with slow speed of
impeller/chopper Off for 10.0 minutes Di
Basic Calcium Phosphate_____23.250________Kg Starch__________26.250___________Kg Lactose_________15.000____________Kg Aerosil
(COLLAIDAL SILICON DIOXIDE)_____0.375____Kg |
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Impeller
Speed (Slow/Fast): __ Slow___ then
__Fast__ Chopper Speed(Off):__Off___
Then___ Slow |
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6.3
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Wet granulation |
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6.3.1 |
Star
RMG at impeller Slow speed and add binder to dry mixed material with fast
impeller and slow chopper speed. Binder addition time shall be 1 to 3
minutes. Continue the process for 15 minutes after complete addition of
binder. Add additional purified
water if required |
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Binder
addition time_______ min. (Limit: About 1 to 3 min.) Wet
Mixing time___________ min(Limit: 15 min) Total
Time:___________ min |
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6.3.3 |
Additional
purified water Qty. ___________L Water addition
time:_________ in Wet mixing time:
_________ min Total time __________
min Impeller Speed
(Slow/Fast)________ Chopper
Speed (Slow/Fast)______ |
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Unload
the granules into FBD bowls with impeller
slow and chopper slow. |
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Step.
No. |
Manufacturing
Instruction |
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6.4
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Drying |
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Air Dry the granules for 10 minutes. |
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Shaking of Bag & put out
the bowls and raking for 1 minutes |
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Drying
Instruction: Dry
the granules at 60°C ± 5°C inlet temperature till the outlet temperature
reached at 45°C ±5°C or the composite sample of dried granules meets the LOD
limit (NMT 2.0% ) of IPQC specs. The indicative parameter for drying process
end point is LOD limit achievement and outlet temperature of about 45°C ±5°C
in drying time of approximately 120 minutes including the raking time. Drying
follows step wise process in FBD. The drying process can be stopped in any
step if the LOD or appropriate outlet temperature is achieved. |
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Collect
the granules and check loss on drying. |
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LOD.
_________________________________%w/w (Limit NMT 2.0 % w/w) |
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Unload
the FBD bowl. |
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6.5
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Milling & sizing |
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Sift
the dried granules through Vibro sifter fitted with 40# mesh. The over sized
granules retained on the 40# mesh should be passed through 8.0 mm screen. Now
pass the sifted granules form multi-mill
fitted with 1.5 mm screen with knife forward direction operated medium speed. |
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Mesh
40# |
Screen
1.5 mm |
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Before Use |
After Use |
Before Use |
After Use |
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Rusted : Yes / No |
Rusted : Yes / No |
Rusted : Yes / No |
Rusted : Yes / No |
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Broken : Yes / No |
Broken : Yes / No |
Broken : Yes / No |
Broken : Yes / No |
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Clean : Yes / No |
NA |
Clean : Yes / No |
NA |
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6.6
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Blending &
Lubrication |
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Transfer
the milled and sized dried granules to blender and add pre-sifted blending
material and blend the materials for 45 minutes at __14__ RPM (to be
reported) Dried
granules________________________kg Ramipril________________________kg
Aerosil
(Colloidal Silicon Dioxide)_______kg Cross
Povidone XL-10 USP28/NF23______kg Magnesium
Sterate_______________kg Sodium
Starch Glyconate__________________________kg Talc_______________________Kg Colour red oxide iron_______________Kg |
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Lubrication |
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Add
pre-sifted magnesium state in blender and blend the material for 5 minutes at
14 RPM (To be reported) Magnesium
Stearate_______________Kg |
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IPQA Shall
collect the sample and send it to QC for analysis |
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Unload
the material in HDPE container with double lined poly bag. |
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6.7 Standard
Specifications
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Sr.
No. |
Parameters |
Requirement |
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1.0
|
Description/ Appearance |
Light
brick red colored capsule shape standard concave tablet having break line on
one side and plain on other side. |
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2.0
|
Punch Size |
13.20
mm x 5.20 mm |
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3.0
|
Weight
of 20 tablets |
5.00
gm ± 2.00% (4.90 to5.10.gm) |
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4.0
|
Avg. weight |
250 mg
± 2.00% (245 to 255 mg) |
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5.0
|
Individual weight variation |
250 mg
± 5% |
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6.0
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Thickness |
3.20 + 0.2 mm |
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7.0
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Hardness |
NLT 4.0 kg/cm2 |
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8.0
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Friability |
NMT 1.0% |
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9.0
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Disintegration Time |
NMT 15 minutes |
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10.0 |
Machine Speed |
To be reported |
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11.0 |
Temperature |
NMT 25
ºC |
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12.0 |
RH |
NMT
55% |
6.8 Batch
Reconciliation
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1.
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Average weight of tablets
(A)=: mg |
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2.
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Standard Yield (B) = Lac |
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3.
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Total weight of compressed
tablets (C) =
Kg. |
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4.
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C Quantity of compressed tablet
in Number (D)= ------------X 1000 X1000 = A |
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5.
|
No. of Tablets rejected during
Metal detection (X): Nos. |
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6.
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No. of Tablets rejected during
Visual Inspection (Y): Nos. |
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7.
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No. of tablet rejected (Z):=
(X+Y)
Nos. |
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8.
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No. of tablet sampled Samples
(E)=
Nos. |
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9.
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(D+E)-Z Yield=------------------------
x 100= (Yield NLT: 98.50%) Std. batch Size |
7.0 BATCH
RECONCILITAION:
Calculate the % yield at various
stages. In case actual yield is out of limit, Officer / Executive /Manager of
production/Packing department shall be fill the deviation form and get it
approved by QA Head
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Sr.
No. |
Stage
of Operation |
Input
(kg) A |
Actual
Wt. (kg) B |
Percentage
(%) B/A x 100 |
Permissible
Yield (%) |
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Lower |
Higher |
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1. |
Dried granules |
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2. |
Lubricated granules |
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3. |
Compressed tablets |
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Actual Wt. of the stage (B)
output / Actual Wt. of stage input (A) x 100 =(B/A)
/ 100= Y% %
ACCOUNTABILITY=to be established % |
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8.0 REVISION
OF HISTORY:
|
Resign
of Revision |
Revision
No. |
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Nil |
000 |
END OF
DOCUMENT
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