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PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES
PROCESS VALIDATION OF PARACETAMOL TABLET
Surendra Nath Yadav*1, Aarti Zanwar1, Jitesh Katewa2, A.K. Seth1 1Department of Pharmacy, Sumandeep Vidyapeeth, Pipariya, Vadodara (Gujarat)- 391760 2Combitic Global Caplet Pvt.Ltd.Sonipet (Harayana)-131001
ABSTRACT In present work, concurrent process validation of Paracetamol Tablet 500 mg, good release tablets was carried out to monitor process parameters in current production batches. In-process quality monitoring of all critical processing steps was done for three production batches, End product testing of current production batches was done to provide documented evidence that manufacturing process is in state of control. Assay for drug content was within the limit of 98%-102% at the dry mixing stage. LOD for the dried granules after wet granulation was within 1.30-1.80%. Assay after lubrication was within the specified limit at different corners in the blender, indicating blend uniformity. Physical parameters like average weight of tablet was found to be 589.5mg-592.5mg, thickness was found to be between 4.0mm-4.4mm, hardness was found to be 3.0kg/cm2-5.0kg/cm2, %friability was between 0.25%-0.41%. disintegration time was 3min -4min, assay of tablets 99.4%-100.0 % for all the three batches of compressed tablets. Temperature monitoring was done throughout the process. Dissolution occurred in buffer up to 30 min. at-50 rpm. , drug release in buffered medium was within the limit of 95%-98% within 30 min. Thickness was 4.09mm-4.24 mm. Uniformity of dosage forms which is found to be (98 % to 102%). Blister strip packing was carried out for the tablets. During packing operation each pack size was checked for physical appearance and sealing quality and found satisfactory. All the tests were found to have satisfactory results. Thus process validation of paracetamol tablet 500mg was successfully completed and found within the specifications. Keywords: Paracetamol Starch, Pyrolidone cellulose Magnesium Stearate & Talcum having Good Release property, Process validation, Concurrent validation INTRODUCTION
A process is a series of interrelated function and activities using a variety of
specified action and equipment which is defined to produce a define result. To validate
the reproducibility and consistency of a process, the full defined process is carried out
using validated equipment, under the established procedure usually at least 3 times.
The process must successfully meet all acceptance criteria each time to consider a
validated process. In many cases, “worst cases” conditions are used for validation to
ensure that process is acceptable in the extreme cases. Sometimes worst condition for the
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system can only really be tested overtime & hence must be evaluated using a rigorous
long term monitoring programme.
Each of these categories may apply to several distinct processes in manufacturing
facilities. Each process to be validated must be specific process clearly described in the
master formula or in the SOP. All the equipment and the process parameter and the
specification in each step must be detailed. Complete description of identity code
number, construction operating capacity, and actual operating range must be defined for
the equipment.
The processing parameter for all step must be sufficiently detailed to permit
complete Reproducibility of the process each time it is performed, such as time period,
pH, volume, temperature, measurement specification, acceptable range etc. The controls
and test and their specification must be defined. The purity profile for the product process
must be defined for the each step.
To be considered validated, the process must consistently meet all the
specification at all stage throughout the procedure at least three times consecutively. It is
very important that the specification for the process undergoing validation be pre-
determine. It is also important that all the critical processing parameter for which
specification has been set; there must be equipment to measure all those parameter for
which specification has been set.
Process validation studies examine a process under normal operating condition to
prove that the process is in control. Once the process has been validated, it is expected
that it remain in control, provided no change are made.
In the event that modification to the process is made, problem occurs or
equipment, or systems, involved in the process are changed, the validation of the process
would be required. Very often validation studies require more measurement than that
required for the routine process. The validation must prove the consistency of the
process, & therefore must assess the efficacy and effectiveness of each step to produce its
intended outcome. [1-4]
MATERIALS AND METHOD
Granulation Raw Material:
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Paracetamol ,Lactose, Pregelatinized Starch ,Polyvinyl Pyrrolidone (Povidone
K30),Purified water
Lubrication Raw Material:
Microcrystalline cellulose,Talcum,Sodium Starch, Glycolate, Colloidal Silicon Dioxide
(Anhydrous) (Aerosil 200), Magnesium Stearate (Veg. Grade)
Manufacturing procedure and schematic diagram of sample location:
Dry Mixing:
Add Paracetamol, Pregelatinized starch, Lactose and Polyvinyl Pyrrolidone previously
weighed and sifted, sequentially in RMG & mixed for 15 min. at slow speed.
Withdraw 2 gm samples by sampling thief at 8 different locations Top left, Top right,
middle, bottom left & bottom right then collected three composite sample from top layer
, middle layer & bottom layer ( Sample No. 6, 7 & 8 ) as shown in below diagram from
RMG after 15 min. mixing interval. Send the sample to Q.C. department for assay
analysis. (Total 8 sample)
Binding:
A. Binder preparation:
1. Take 15.0 Lt. purified water in to cleaned SS vessel.
Top Left (1) Top Right (2)
Bottom Left (4)
Bottom Right (5)
Middle (3)
Fig:1 Rapid Mixer Granulator (RMG)
COMPOSITE SAMPLE (6) TOP LAYER
COMPOSITE SAMPLE (8) BOTTOM LAYER
COMPOSIT SAMPLE (7) MIDDLE LAYER
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2. Add starch slurry and dissolved Povidone K 30 in above solution under
continuous stirring and heat to prepare starch paste.
B. Binding:
1. Start RMG containing dry mixed powder at slow speed, Add binder into RMG.
2. Mixed under slow speed for 20 - 22 minutes. Rinse the binder vessel with 0.5 Lt.
of purified water and added to RMG, ran the chopper during the mixing at slow
speed for 3 - 4 minutes. Till granulation end point is reached to get required
consistency of dough mass.
C. Wet Milling:
Passed the wet mass through conical mill using 15.0 mm screen. Collected the milled
granules in to FBD bowl.
Drying:
Performed drying in FBD: Loaded the wet mass of respective lot in FBD bowl. Dried
the wet mass at ambient temperature for 15 min. Rack the mass of the bowl. Then dried
at 40°C - 50°C inlet temperature with intermittent raking till water content of granules
obtained must not be more than 7.0 – 4.0 %. After drying collected 5 gm by sampling
thief sample at 5 different locations from the FBD bowl as per given below.
After drying sifted the granules through # 18 sieves using vibratory sifter and over
size granules passed through oscillating Granulator using 1.2 mm S.S. screen.
After sifting and sizing loaded the Granules in octagonal Blender.
Lubrication:
Fig:2 FLUIDISED BED DRYER (FBD)
Top left(1)
Top right(2)
Bottom left (4)
Bottom Right(5)
Middle (3)
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Loaded the granules in octagonal blender and mix for 5 min. collecedt the
composite sample by sampling thief from 5 different locations and check LOD. Add all
lubricants previously weighed and sifted (except Magnesium Stearate) & mix for 15
minute mixing. Add sifted Magnesium Stearate & continue mixing for 3 min.
Sample Position:
Sample location for Lubrication stage
Left Center Right
Top Layer 1 2 3
Middle layer 4 5 6
Bottom Layer 7 8 9
Sample locations for lubrication stage
Collected 2 gm samples by sampling thief from 9 different locations from
octagonal blender shown above after 15 min. mixing (Without addition of Magnesium
stearate) & after addition of Magnesium stearate mix for 3 min. collected one composite
Sample (approx. 100 gm) from 9 different locations. For analysis of loss on drying, Bulk
density and sieve analysis (for information) after lubrication unloaded the granules in SS
IPC.
Compression:
Set the Compression Machine on following parameter and compressed the tablet
Fig:3 OCTAGONAL BLENDER
å ç é
è ê ë
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Table;1 parameters of compression stage
Blister strip Packing Machine setting and operation details :
Set the machine as per standard operating procedure. After seating the machine, operate
on selected temperature & speed. Following parameters checking during striping.
• Appearance of strips : Aesthetically good legible over coding, no colors
smudging of strips.
• Sealing and cutting : Proper sealing, uniform cutting.
• Cut pocket : Free from hollow pocket, no damage pocket.
• Leak test : No one pocket should wet.
• Appearance of tablet
(after strip packing)
: Appearance of tablet should match as per description of
tablet.[5-14]
RESULTS & DISCISSION
The Manufacturing of paracetamol Tablet-500mg is validated successfully considering
the following Parameter.
S. No. Tablet Parameter Set value
1 Appearance White round, flat, uncoated tablets with break line on one side.
2 Average weight of tablet 590 mg ± 2% [578.2 mg to 601.8 mg]
3 Weight of 20 tablet 11.800 gm ± 2 % [11.564 gm to 12.036 gm]
4 Uniformity of weight ± 5 % of Average weight
5 Dimension 13.55 X 4.20 ±0.2 mm
6 Thickness 4.0 to 4.4 mm
7 Hardness 3.0 –5.0 Kg /cm2
8 Friability NMT 1.0 % w/w
9 Dissolution NLT 80 %.
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S.No. Process stage Observation
1.0 Dry mixing : Dry mixing performed in RMG for 15 min.
2.0 Wet mixing
and Binding
: Wet mixing performed for 20 - 22 minute at slow speed,
keeping the chopper ON for 3 - 4 min.
Wet milling done through Co mill using 15.0 mm screen.
3.0 Drying : Drying performed in fluid bed dryer.
Initial drying at ambient Temperature for 15 min.
Final drying at 40 - 50º C Temperature for 25 – 50 min.
4.0 Sifting and
sizing of dried
granules
: Dried granules sifted through 16 mesh sieve using
vibratory sifter, and pass the over sized granules through
1.2 mm ss screen through Oscillating granulator.
5.0 Lubrication : Lubrication performed in Octagonal Blender.
Unlubricated granules mixed for 5 min.
Lubricated granules mixed without Magnesium Stearate
for 15 min.
Lubricated granules mixed with Magnesium Stearate for
3 min.
6.0 Compression : Compression performed on single rotary press at
30 ± 5 [25 to 35] RPM.
7.0 Blister strip : Blister Strip sealing : ( For 47525)
Blister forming roller Temperature Observed between
120 ± 20 º C and Counter sealing roller Temp. Observed
between 220 ± 20 º C at speed 40 ± 10 cuts/ min.
Blister Strip sealing : ( For 35950)
Blister forming roller Temperature Observed between
150 ± 20 º C and Counter sealing roller Temp. observed
between 220 ± 20 º C at speed 40 ± 10 cuts/ min.
Status of Qualification:
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To be used in manufacturing of Paracetamol Tablet-500mg shall be described as
per the following table:
Table: 2 Status of Qualification
S. No. Name of the Equipment Qualified (Yes / No)
1. Vibratory sifter YES
2. Rapid Mixer Granulator YES
3. Steam Kettle YES
4. Multi mill YES
5. Fluid Bed Dryer YES
6. Oscillating Granulator YES
7. Octagonal Blender YES
8. Compression Machine YES
9. Blister strip machine YES
10. PLC validation of Critical equipment YES
Status of Preventive Maintenance:
The status of the preventive maintenance of various equipment shall be described as per the
following table:
Table: 3 Status of Preventive maintainance
S. No Name of the Equipment Preventive maintenance Status
1. Vibratory sifter Conforms
2. Rapid Mixer Granulator Conforms
3. Steam Kettle Conforms
4. Multi mill Conforms
5. Fluid Bed Dryer Conforms
6. Oscillating Granulator Conforms
7. Octagonal Blender Conforms
8. Compression Machine Conforms
9. Blister strip Machine Conforms
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Status of Calibration:
The status of calibration of different gauges, thermometer, sensors, balances, etc. shall be
described as per the following table:
Table: 4 Status of Calibration
S. No
Measuring Device Calibration Status
1. Weigh Balance (Granulation) Calibrated
2. Thermo Hygrometer (Granulation) Calibrated
3. FBD outlet Temperature gauge Calibrated
4. FBD inlet Temperature gauge Calibrated
5. IR Moisture balance Calibrated
6. Thermo Hygrometer (Compression) Calibrated
7. Balance (IPQC) Calibrated
8. Vernier Calipers Calibrated
9. Hardness Tester Calibrated
10. Friability Apparatus Calibrated
11. Disintegration Test Apparatus Calibrated
12. Dissolution Calibrated
13. Thermo Hygrometer (Blister packing) Calibrated
14. Blister strip Machine Temperature gauge Calibrated
15. Blister strip Machine Pressure gauge Calibrated
Manufacturing process observation and Analytical Results:
Table: 5 Dry mixing stage observation
Equipment : Rapid Mixer Granulator (RMG)
Dry mixing Time : 15 min
Speed : At slow speed
Batch No. X Y Z
From To From To From To
Total Mixing Time
10:40 10:55 16:10 16:25 10:20 10:35
15 min. 15 min. 15 min.
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Table: 6 Analytical results
Paracetamol content in dry mix : Acceptance criteria : 98.0 % to 102.0%
Sample Identification
Sample Location Batch No.
X Y Z
Sample (S1) Top Left 99.1 99.0 98.4 Sample (S2) Top Right 99.1 99.8 99.2 Sample (S3) Middle 99.2 99.6 99.7 Sample (S4) Bottom Left 99.0 99.5 99.8 Sample (S5) Bottom Right 99.4 99.6 99.6
Sample (S6) Composite Top
Layer 99.4 99.8 100.5
Sample (S7) Composite Middle
Layer 99.2 99.5 101.0
Sample (S8) Composite Bottom
Layer 99.1 99.9 99.7
Average --- 99.19 99.59 99.74 RSD --- 0.15 0.28 0.78
Table: 7 Inprocess checks for Binder
S. No.
Parameter Observation
Batch No. X Y Z
1. Transfer of starch slurry Done Done Done
2. Addition and dissolution of Povidone K
30 Done Done Done
Inprocess checks for wet mixing and binding stage observation:
Table: 8 Inprocess checks for wet mixing and binding
S. No.
Parameter Batch No.
Observation X Y Z From To From To From To
1 Wet Mixing at slow
speed for 20 - 22 min. 11:10 11:30 16:30 16:50 10:40 11:00
Satisfactory 2
Keeping chopper ON at slow speed for 3 - 4
min. 11:35 11:38 16:55 16:58 11:05 11:08
3 Quantity of extra Purified water (If
required) - - - Satisfactory
4
Ampere load at the end point of granulation
(For data Collection)
38.4 37.7 35.8 Satisfactory
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Milling stage Observation:
Table: 9 Milling stage Observation
Equipment Screen
size
Observation Batch No.
X Y Z
CO – Mill 15.0 mm
Passed the wet mass through co-
mill using 15.0 mm screen.
Passed the wet mass through co-
mill using 15.0 mm screen.
Passed the wet mass through co-mill using 15.0 mm
screen.
Drying stage Observation:
Table: 10 Drying stage Observation
Batch No.
Initial Drying at Ambient Temperature
15 min.
Inlet Temp. (40 – 500C)
*Out let Temp.
Final Drying for 25 – 50 min. Remark
From TO Time From TO Time
X 12:20 12:35 15
min. 450c 290c
12:45 13:05
13:00 13:30
15 min 25 min
Satisfactory
Y 17:15 17:30 15
min. 450c 280c
17:35 18:00
17:50 18:20
15min 20 min
Satisfactory
Z 11:30 11:45 15
min. 450c 290c 11:55 12:35 40 min Satisfactory
Water content result after drying:
Table: 11 Water content result after drying
Loss on drying of dried Granules Acceptance criteria : 1.0 – 2.0 %
Batch No. Top Left
Top Right
Middle Bottom
Left Bottom Right
% RSD (for
information)
X 1.34% 1.38% 1.36% 1.41% 1.40% 0.506
Y 1.54% 1.51% 1.58% 1.61% 1.59% 0.516
Z 1.43% 1.42% 1.51% 1.55% 1.49% 0.606
Granules sifting and sizing observation:
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Table: 12 Granules sifting and sizing observation
Equipment Process Sieve /
Screen size
Observation Batch No.
X Y Z
Vibratory sifter
Sifting 16
Sift the dried material
through 16 mesh using
vibratory sifter.
Sift the dried material
through 16 mesh using
vibratory sifter.
Sift the dried material
through 16 mesh using
vibratory sifter.
Oscillating Granulator
Sizing 1.5 mm
Passed the retention
through OG using 1.5 mm
ss screen.
Passed the retention
through OG using 1.5 mm
ss screen.
Passed the retention
through OG using 1.5 mm
ss screen.
Table: 13 Water content results after sifting and sizing
S.
No.
Test to be performed
(composite sample) Limit
Results (for information) Batch No.
X Y Z
1 Loss on drying 1.0 – 2.0 % 1.41% 1.54% 1.49%
Table: 14 Lubrication Stage Observation
Equipment : Octagonal Blender
Process stage
Batch No. X Y Z
From To From To From To
Unlubricated granules mix for 5 min.
10:20 1025 12:40 12:45 16:50 16:55
Lubricated granules mix for 15 min.
10:40 10:55 13:40 13:55 17:20 17:35
Total mixing time 20 min. 20 min. 20 min.
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Analytical Results:
Table: 15 Analytical Results of samples after lubrication
Paracetamol content in Lubricated Granules :
Acceptance criteria: 98.0 % to 102.0%
Sample No. Sample ID Batch No.
X Y Z
Sample 1(S1) Top Left 99.5 99.8 99.9 Sample 2 (S2) Top Center 99.7 99.7 99.6
Sample 3 (S3) Top Right 99.5 99.7 99.6 Sample 4 (S4) Middle Left 99.6 99.9 99.5
Sample 5 (S5) Middle Center
99.8 99.5 99.6
Sample 6 (S6) Middle Right 100.0 99.2 99.4 Sample 7 (S7) Bottom Left 98.4 99.4 99.5
Sample 8 (S8) Bottom Center
99.7 99.8 99.5
Sample 9 (S9) Bottom Right 99.4 100.0 99.3 Average --- 99.51 99.67 99.54
RSD (NMT 2%)
--- 0.46 0.26 0.17
Table: 16 Test Results after lubrication
Process Stage
Tests on Composite sample
criteria Results
Batch No. X Y Z
After Lubrication
Bulk Density in gm / ml
Untapped For
Information 0.5 g/ml 0.5 g/ml 0.5 g/ml
Tapped For
Information 0.7 g/ml 0.7 g/ml 0.7 g/ml
Sieve analysis in %
# 20 For
Information 70.7% 71.1% 71.8%
# 40 For
Information 49.0% 49.5% 52.2%
# 60 For
Information 38.7% 41.7% 41.6%
# 80 For
Information 33.5% 35.1% 34.4%
# 100 For
Information 29.7% 30.7% 29.0%
Water content 1.0 – 2.0 % 1.45% 1.61% 1.59% Assay 98 % to 102 % 99.0% 99.9% 99.5%
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Observation and Results of Uncoated Tablets:
Different time
Table: 17 Observations for Physical Parameter of Batch X (Uncoated)
[A] Batch No. : X
Physical parameters
Acceptance criteria
Initial Middle End Date : 11/01/11 Date : 11/01/11 Date : 11/01/11
Time : 09:40 Time : 12:15 Time : 15:10 RHS LHS RHS LHS RHS LHS
1-Appearance :
* Conforms Conforms - Conforms - Conforms -
2-**Wt of Tablet in gm.
[11.80/20 Tabs.]
11.564 gm to 12.036 gm
11.820 - 11.800 - 11.800 -
3-Average weight
590 mg ± 2% [11.564 gm
to12.036 gm] 591.0 590.0 - 590.0 -
4-Uniformity of weight :
± 5% of Average weight
590 - 584 - 582 - 588 - 590 - 595 - 593 - 589 - 594 - 595 - 596 - 592 - 597 - 593 - 586 - 587 - 592 - 582 - 588 - 597 - 592 - 593 - 588 - 586 - 587 - 596 - 592 - 590 - 587 - 591 - 593 - 584 - 592 -
594 - 594 - 597 -
587 - 586 - 580 - 594 - 583 - 588 - 587 - 593 - 583 - 595 - 590 - 592 - 591 - 591 - 598 - 592 - 587 - 588 - 583 - 584 - 587 - 592 - 596 - 594 -
- - - - - - - - - - - - - - - - -
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- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Minimum 583 - 584 - 580 - Maximum 597 - 597 - 598 -
Wt. Variation ± % -1.35 - -1.70 - - - 1.02 - 1.18 - 1.36 -
Physical parameter &
Test procedure No.
Acceptance criteria
Initial Middle End
RHS LHS RHS LHS RHS LHS
5-Thickness :
4.0 – 4.4 mm
4.11 - 4.22 - 4.25 - 4.32 - 4.15 - 4.13 - 4.21 - 4.26 - 4.32 - 4.32 - 4.27 - 4.18 - 4.11 - 4.34 - 4.26 - 4.24 - 4.13 - 4.15 - 4.15 - 4.12 - 4.31 - 4.12 - 4.21 - 4.22 - 4.34 - 4.35 - 4.23 - 4.13 - 4.13 - 4.12 -
Range in mm 4.11– 4.34 mm 4.12 – 4.35 mm 4.12 – 4.32 mm
6-Hardness :
3.0 – 5.0 Kg / cm 2
4.1 3.1 3.2 3.6 4.2 4.3 4.2 4.8 3.6 4.4 3.4 4.5 4.8 3.5 4.4 4.2 3.6 3.2 3.3 4.3 3.5 4.1 - 3.6 - 3.4 - 3.5 - 4.7 - 4.5 - 3.6 - 3.5 - 3.8 -
Range in Kg / cm 2 3.3 – 4.8Kg/cm2 3.1 – 4.8Kg/cm2 3.2 – 4.5Kg/cm2
7-Friability : Wt. of 12
Tablets before Friability
7.080. - 7.092 - 7.068 -
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Wt. of Tablets after Friability
7.052 - 7.074 - 7.044 -
Wt. of Loss in gm.
0.28 - 0.018 - 0.024 -
NMT 1.0 % w/w
0.40% - 0.25% - 0.34% -
8-Disintegration
Time :
NMT 15 min.
7’38” – 10’10” 08’05” – 11’20” 07’55” – 11’05”
9-Assay: 98 % to 105 % 99.4% 99.1% 100.3%
Dimension check at the initial stage during compression :
10-
Dimension:
13.55 x
4.20 mm
13.52x4.28 13.53x4.23 13.55x4.23 - - -
13.54x4.28 13.52x4.25 13.54x4.31 - - -
13.52x4.35 13.52x4.22 - - - -
3.52x4.27 13.55x4.26 - - - -
13.54x4.35 13.54x4.24 - - - -
13.56x4.28 13.56x4.25 - - - -
13.52x4.26 13.52x4.23 - - - -
13.55x4.34 13.53x4.23 - - - -
13.52x4.25 13.53x4.21 - - - -
Range in mm 13.52x4.21 - 13.56x4.34
**Equal to no. of punches
* Conforms – White round flat uncoated tablets with break line on one side. Free
from rough surface, Hairline cracks, sticking, mottling, chipped edges
etc.
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Table: 18 observations for Physical Parameter of Batch Y (Uncoated)
[B] Batch No. : Y
Physical parameters
Acceptance criteria
Initial Middle End Date : 12/01/11 Date : 12/01/11 Date : 12/01/11
Time : 09:50 Time : 12:20 Time : 15:25 RHS LHS RHS LHS RHS LHS
1-Appearance :
* Conforms Conforms - Conforms - Conforms -
2-**Wt of Tablet in gm.
[11.84/20 Tabs.]
11.566 gm to 12.032 gm
11.840 - 11.820 - 11.780 -
3-Average weight
590 mg ± 2% [11.566
to12.032 gm] 592.0 - 591.0 - 589.0 -
4-Uniformity of weight :
± 5% of Average weight
594 - 590 - 591 - 590 - 583 - 592 - 593 - 589 - 588 - 584 - 593 - 586 - 596 - 596 - 581 - 590 - 584 - 593 - 591 - 598 - 586 - 590 - 586 - 590 - 596 - 593 - 598 - 591 - 596 - 586 - 601 - 587 - 590 - 588 - 591 - 593 - 588 - 590 - 588 - 596 - 583 - 586 - 593 - 594 - 587 - 594 - 587 - 593 - 590 - 588 - 590 - 594 - 592 - 588 - 590 - 596 - 589 - 591 - 584 - 586 -
- - - - - - - - - - - - - - - - - - - - -
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- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Minimum 584 - 583 - 581 - Maximum 601 - 598 - 598 -
Wt. Variation ± % -1.35 - -1.35 - -1.36 - 1.52 - 1.18 - 1.52 -
Physical parameter &
Test procedure No.
Acceptance criteria
Initial Middle End
RHS LHS RHS LHS RHS LHS
5-Thickness :
4.0 – 4.4 mm
4.24 - 4.32 - 4.25 - 4.13 - 4.16 - 4.37 - 4.31 - 4.21 - 4.19 - 4.12 - 4.35 - 4.22 - 4.30 - 4.26 - 4.38 - 4.23 - 4.22 - 4.12 - 4.35 - 4.33 - 4.14 - 4.30 - 4.21 - 4.21 - 4.14 - 4.14 - 4.28 - 4.26 - 4.23 - 4.31 -
Range in mm 4.12 – 4.34 mm 4.14 – 4.35 mm 4.12 – 4.38 mm
6-Hardness : 3.0 – 5.0 Kg /
cm 2
3.6 - 3.4 - 3.5 - 3.2 - 4.2 - 3.8 - 3.5 - 4.7 - 3.5 - 4.1 - 4.5 - 4.5 - 3.5 - 3.6 - 4.1 - 4.4 - 3.8 - 3.5 - 3.2 - 3.4 - 3.5 - 3.3 - 3.5 - 4.6 - 3.6 - 3.6 - 3.8 - 3.8 - 4.5 - 4.5 -
Range in Kg / cm 2 3.2 – 4.4Kg/cm2 3.4 – 4.7Kg/cm2 3.5 – 4.6Kg/cm2
7-Friability :
Wt. of 12 Tablets before
Friability 7.104 - 7.092 - 7.080 -
Wt. of Tablets after Friability
7.078 - 7.063 - 7.043 -
Wt. of Loss in gm.
0.026 - 0.029 - 0.037 -
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www.pharmasm.com IC Value – 4.01 47
NMT 1.0 % w/w
0.37% - 0.41% - 0.52% -
8-Disintegration
Time :
NMT 15 min.
06’45” – 07’15” 05’56” – 06’40” 06’15” – 07’15”
9-Assay: 98.0 % to 102.0
% 99.6% 100.5% 99.7%
Dimension check at the initial stage during compression :
10-
Dimension:
13.55 x
4.20 mm
13.53x4.22 13.56x4.24 13.52x4.24 - - -
13.56x4.31 13.56x4.28 13.53x4.25 - - -
13.52x4.23 13.52x4.23 - - - -
13.54x4.25 13.57x4.29 - - - -
13.56x4.31 13.56x4.27 - - - -
13.53x4.23 13.53x4.22 - - - -
13.55x4.24 13.51x4.30 - - - -
13.53x4.24 13.54x4.21 - - - -
13.51x4.23 13.56x4.25 - - - -
Range in mm 13.51x4.2 1– 13.57x4.31
**Equal to no. of punches
* Conforms – White round flat uncoated tablets with break line on one side. free
from rough surface, Hairline cracks, sticking, mottling, chipped edges
etc.
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Table: 19 observations for Physical Parameter of Batch Z (Uncoated)
[C] Batch No. : Z
Physical parameters
Acceptance criteria
Initial Middle End Date : 13/01/11 Date : 13/01/11 Date : 13/01/11
Time : 09:45 Time : 12:15 Time : 15:20 RHS LHS RHS LHS RHS LHS
1-Appearance :
* Conforms Conforms - Conforms - Conforms -
2-**Wt of Tablet in gm.
[11.82/20 Tabs.]
11.562 gm to 12.034 gm
11.800 - 11.780 - 11.820 -
3-Average weight
590 mg ± 2% [11.562
to12.034 gm] 590 - 589 - 591 -
4-Uniformity of weight :
± 5% of Average weight
580 - 592 - 592 - 594 - 588 - 590 - 595 - 590 - 587 - 598 - 594 - 590 - 585 - 598 - 591 - 592 - 590 - 588 - 582 - 589 - 593 - 586 - 592 - 590 - 578 - 590 - 592 - 590 - 600 - 590 - 588 - 582 - 591 - 598 - 588 - 588 - 586 - 589 - 594 - 595 - 590 - 591 - 585 - 585 - 592 - 600 - 589 - 589 - 594 - 580 - 592 - 601 - 584 - 598 - 582 - 588 - 594 -
593 - 582 - 592 -
- - - - - - - - - - - - - - - - - -
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- - - - - - - - - - - - - - - - - - - - - - - - - - -
Minimum 578 - 580 - 587 - Maximum 601 - 600 - 598 -
Wt. Variation ± % -2.03 - -1.53 - -0.68 - 1.7 - 1.87 - 1.18 -
Physical parameters
Acceptance criteria
Initial Middle End RHS LHS RHS LHS RHS LHS
5-Thickness :
4.0 – 4.4 mm
4.36 - 4.12 - 4.30 - 4.22 - 4.24 - 4.13 - 4.38 - 4.29 - 4.12 - 4.21 - 4.17 - 4.22 - 4.12 - 4.32 - 4.37 - 4.13 - 4.11 - 4.31 - 4.31 - 4.20 - 4.20 - 4.31 - 4.12 - 4.17 - 4.20 - 4.36 - 4.15 - 4.29 - 4.20 - 4.27 -
Range in mm 4.12 – 4.38 mm 4.11 – 4.36 mm 4.12 – 4.37 mm
6-Hardness :
3.0 – 5.0 Kg / cm 2
3.1 - 3.2 - 3.2 - 3.5 - 3.6 - 3.6 - 4.2 - 3.2 - 4.1 - 4.5 - 4.2 - 4.5 - 4.1 - 4.8 - 3.9 - 3.5 - 3.7 - 3.4 - 4.1 - 3.7 - 4.1 - 4.6 - 3.2 - 4.2 - 3.8 - 4.2 - 3.7 - 3.4 - 3.5 - 4.1 -
Range in Kg / cm 2 3.1 – 4.6Kg/cm2 3.2 - 4.8 Kg/cm2 3.2 – 4.5 Kg/cm2
7-Friability :
Wt. of 12 Tablets before
Friability
7.104 - 7.080 - 7.056 -
Wt. of Tablets after
Friability 7.077 - 7.047 - 7.036 -
Vol-3, Issue-3, July-2012 ISSN: 0976-7908 Yadav et al
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Wt. of Loss in gm.
0.027 - 0.033 - 0.020 -
NMT 1.0 % w/w
0.38% - 0.47% - 0.28% -
8-Disintegration
Time :
NMT 15 min.
05’42” – 07’02” 06’37” – 08’11” 07’04” – 08’32”
9-Assay: 98.0%
to102.0 % 99.5% 99.8% 99.3%
Dimension check at the initial stage during compression :
10-
Dimension:
13.55 x
4.20 mm
13.55x4.33 13.54x4.31 13.55x4.30 - - -
13.51x4.27 13.51x4.29 13.56x4.25 - - -
13.53x4.28 13.55x4.28 - - - -
13.55x4.31 13.52x4.25 - - - -
13.54x4.27 13.56x4.31 - - - -
13.51x4.28 13.51x4.27 - - - -
13.55x4.30 13.54x4.25 - - - -
13.57x4.29 13.55x4.25 - - - -
13.52x4.27 13.53x4.27 - - - -
Range in mm 13.51x4.25 – 13.57x4.33
**Equal to no. of punches
* Conforms – White round flat uncoated tablets with break line on one side. free
from rough surface, Hairline cracks, sticking, mottling, chipped edges
etc.
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Summary of uncoated tablets:
Table: 20 Summary of uncoated tablets
Parameters Acceptance
criteria Batch No.
X Y Z
Appearance *Conforms Conforms Conforms Conforms
Average weight
590 mg ± 2% [578.2 to 601.8
mg] 590 mg 589 mg 591 mg
Uniformity of weight
± 5% of Average weight
560.5 mg to 619.5 mg
559.6 mg to 618.5 mg
561.5 mg to 620.6 mg
Dimension 13.55 X4.20 ±0.2
mm 13.54X4.10mm 13.52X4.09mm 13.57X4.24mm
Thickness 4.0 to 4.4 mm 4.10 mm 4.09 mm 4.24 mm
Hardness 3.0 to 5.0 Kg /
cm 2 3.0 – 4.0 3.5- 4.5 3.0 – 4.5
Friability NMT 1.0 % w/w 0.25 % 0.38 % 0.41 %
Disintegration time
NMT 15 min. 3 min 4min 3min
* Conforms – White round flat uncoated tablets with break line on one side.
Blister strip Packing Machine setting and operation details:
Equipment Name: Blister machine
Acceptance Criteria:
(A)Description: White round flat uncoated tablets with break line on one side.
(B) Leak Test: There should not be any leakage in any of the strips. (Pocket)
Blister Strip packing Inprocess monitoring every two hours from the starting of the
stripping
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Table: 21 Blister packing In-process monitoring Parameter
Parameter
Batch No X Y Z
Initial Middle End Initial Middle End Initial Middle End
Blister Forming
Plate Temp. 1280c 1280c 1270c 1280c 1280c 1280c 1660c 1650c 1650c
Counter sealing Roller Temp.
2000c 2000c 2000c 2000c 2000c 2000c 2000c 2000c 2000c
Machine speed in
CPM 40 42 42 40 40 40 40 42 40
Sample taken
(100strips) 100 100 100 100 100 100 100 100 100
Appearance of strips
Ok Ok Ok Ok Ok Ok Ok Ok Ok
Sealing & cutting Quality
Ok Ok Ok Ok Ok Ok Ok Ok Ok
Cut Pocket Not
found Not
found Not
found Not
found Not
found Not
found Not
found Not
found Not
found
Leak Test Not
found Not
found Not
found Not
found Not
found Not
found Not
found Not
found Not
found Appearance of Tablets
Ok Ok Ok Ok Ok Ok Ok Ok Ok
observations & Inprocess checks of packing operation:
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Table: 22 In-process checks of Final Packing Operation
Inprocess parameter
Batch No.
Stage Quality of strips
Coding of batch details
Over printing on Show
Box
Strips packed
in a Show Box
No. of show box pack in
shipper
Over printing
batch details
on shipper
label
X
Initial S S S
10x10T 100x10x10T S
Middle S S S 10x10T 100x10x10T S
End S S S 10x10T 100x10x10T S
Y
Initial S S S 10x10T 100x10x10T S
Middle S S S 10x10T 100x10x10T S
End S S S
10x10T 100x10x10T S
Z
Initial S S S 10x10T 100x10x10T S
Middle S S S 10x10T 100x10x10T S
End S S S 10x10T 100x10x10T S
S = Satisfactory
Observations & Acceptance Criteria of finished products (uncoated tabs.)
Table: 23 Observations & Acceptance Criteria of finished products
S. No
Test Acceptance Criteria Batch No.
X Y Z
1. Appearance White round flat Uncoated tablets with break line on one side.
Conforms Conforms Conforms
2. Identification
In the assay, the test solution shows the maxima as the same wave length as than that of the standard solution.
Conforms Conforms Conforms
3. Average weight
590 mg ± 2 % 590 mg 589 mg 591 mg
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4. Uniformity of weight
Within ± 5 % of average weight.
With in limits With in limits
With in limits
5. Friability NMT 1.0 % Conforms Conforms Conforms
6. Dissolution NLT 80 % In 30 min. MT 95.0 % MT 98.0%
MT 97.0%
7. Assay : Paracetamol Tablet 500 mg
98.0 % to 102.0% 100.0% 99.4% 99.8%
CONCLUSION
All the analytical data derived during process validation of Paracetamol Tablet-
500 mg with reference to TMD. (Technical Manufacturing Document)
The results from the analytical data of process validation of Paracetamol tablet
500 mg was excellent and very near to true values. These results prove that the process is
validated.
ACKNOWGEMENT
It gives me an immense pleasure to thank my guide Mrs.Aarti Zanwar and
Industrial Guide Mr. Jitesh Katewa & Dr A.K Seth, Director, Department of Pharmacy,
Sumandeep Vidyapeeth. I am also Thankful to Combitic Global Caplet Pvt.LTd Sonipet
(Harayana) for Providing the facility to Perform my Project Work.
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For Correspondence: Surendra Nath Yadav Email: [email protected]