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Chaudhari et al. World Journal of Pharmaceutical Research
PROCESS VALIDATION OF SOLID ORAL DOSAGE FORM OF
TRANDOLAPRIL TABLET 1 MG
Monika Ola, Rajveer Bhaskar, Pratiksha Rathi and Lalita Chaudhari*
1Department of Pharmaceutics and Pharmaceutical Quality Assurance, R. C. Patel Institute of
Pharmaceutical Education and Research, Karwand Naka.
2Shirpur, Dhule District, Maharashtra 425 405, India.
3Department of Quality Assurance ACP, Chikhli, Buldana District, Maharashtra 443201,
India.
ABSTRACT
The concept of validation was first proposed by Food and Drug
Administration officials in 1970 in order to improve the quality of
pharmaceuticals as well as different life saving products. Process
validation is important to establish documented evidence which
provides a high degree of assurance that a specific process for
manufacturing of tablets will consistently produce a product meeting
its pre-determined specifications and quality attributes. This study
contributes to validation of all the steps while manufacturing of
Trandolapril tablets. The different steps include in this study are,
Sifting, Milling, Dry mixing, Granulation, Drying, Blending,
Lubrication, compression, and Packing. While validation of all the
steps different critical parameters were studied and found satisfactory
as it fulfills acceptance criteria. We mainly focused on validation
parameters like, Particle size distribution while sifting and milling,
blend uniformity while blending and lubrication, LOD while drying,
hardness, thickness, disintegration, dissolution, friability, average
weight, group weight are studied after compression, Packing material were also checks for its
quality. All results were found within acceptance limit.
KEYWORDS: Solid Dosage form, Process Validation, Trandolapril Tablet, Quality
management.
World Journal of Pharmaceutical Research SJIF Impact Factor 8.074
Volume 7, Issue 11, 1270-1305. Research Article ISSN 2277– 7105
Article Received on
12 April 2018,
Revised on 02 May2018,
Accepted on 23 May 2018
DOI: 10.20959/wjpr201811-12544
*Corresponding Author
Lalita Chaudhari
Department of
Pharmaceutics and
Pharmaceutical Quality
Assurance, R. C. Patel
Institute of Pharmaceutical
Education and Research,
Karwand Naka.
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INTRODUCTION
Validation has proven to be an important tool for quality management of pharmaceuticals.
According to ISO 9000:2000, Validation is defined as,
“Confirmation, through the provision of objective evidence, that the requirements for a
specific intended use or application have been fulfilled”. In contrast with Verification,
Validation rather focuses on the question whether a system can perform its desired functions.
This review is an attempt to prove that it as essential tool for quality management in
pharmaceuticals industry.
Validation is concepts that have been evolving continuously since its first formal appearances
in United States in 1978. The concept of validation has expanded through the years to
encompass a wide range of activities from analytical methods used for the quality control of
drug substances and products to computerized system for clinical trial, labeling or process
control. The word “validation” simply means assessment of validity or action of proving
effectiveness.
Importance of Validation[2]
The most compelling reasons to optimize and validate pharmaceutical production and
supporting processes are quality assurance and cost reduction. The basic principles of quality
assurance have as their goal and the production of articles that are fit for their intended use.
It deepens the understanding of processes, decreases the risks, processing Problems, and
assures the smooth running of the process.
It decreases the risks of defect costs.
It decreases the risks of regulatory non-compliance.
A fully validated process may require less in- process control and end product testing.
It optimizes the process.
It gives assurance of quality and safety.
Need of Validation[3,4]
If Process validation does not carried out then following problems can occur. i.e.
Low process capability
1. Scrap, Rework, or Recall
2. Protracted production cycle times and low capacity utilization.
3. Resolution of process related problems slow and difficult.
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4. High cost of compliance.
There is a Risk of
1. Drug shortages.
2. Releasing a poor quality product.
3. Recall.
4. Delay in approval of new drugs.
5. Quality problems confounding clinical trial data.
So, to minimize these problems Process validation is carried out.
Major Phases in Validation[2,5]
The activities relating to validation studies may be classified into three
Phase 1: This is the pre- validation Qualification Phase which covers all activities relating to
product research and development, formulation pilot batch, establishing stability condition
and storage, and handling of in-process and finished dosage forms, equipment qualification,
installation qualification, master production document, operational qualification and process
capacity.
Phase 2: This is the process validation phase. It is designed to verify that all established limit
of the critical process parameter are valid and that satisfactory product can be produced even
under the worst condition.
Phase 3: Known as the validation Maintenance phase, it requires frequent review of all
process related documents, including validation of audit reports, to assure that there have
been no changes, deviations, failures and modifications to the production process and that all
standard operating procedures (SOPs), including change control procedures, have been no
changes/deviations that should have resulted in requalification and revalidation. A careful
design and validation of systems and process controls can establish a high degree of
confidence that all lots or batches produced will meet their intended specifications. It is
assumed that throughout manufacturing and control, operations are conducted in accordance
with the principle of good manufacturing practice (GMP) both in general and in specific
reference to sterile product manufacture.[6]
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Scope of Validation[2,7]
Pharmaceutical validation is a vast area of work and it practically covers every aspects of
pharmaceutical processing activates; hence defining the scope of validation becomes a really
difficult task. A systematic look at the pharmaceutical operations will point out at least the
following areas for pharmaceutical validation, e.g. Instrument Calibration, Process Utility
services, Raw materials, Packaging materials, Equipment, Facilities, Manufacturing
operation, Product Design, Cleaning, Operators etc.
Process Validation[2,14]
“Process validation” is defined by the U. S. Food and Drug Administration (USFDA) as,
“Establishing documented evidence which provides a high degree of assurance that a specific
process will consistently produce a product meeting its pre-determined specifications and
quality attributes”
Types Of Process Validation[6,11,12,19,7,8,21]
There are three types of process validation as follows
1) Prospective Validation: It would normally be expected that process validation be
completed prior to the distribution of a finished product that is intended for sale.
2) Concurrent Validation: Where this is not possible, it may be necessary to validate
processes during routine production.
3) Retrospective Validation: Processes which have been in use for some time without any
significant changes may also be validated according to an approved protocol.
Different Steps of Process Validation for Tablet Manufacturing
Sifting, Mixing & Blending, Granulation, Drying, Milling, Lubrication, Compression are the
steps which are important to validate during process validation of tablet dosage form
including all the critical parameters of each step.
MATERIALS AND METHOD
Materials
All material used of USP/NF/IH grade and chemicals used in the analysis in the study were of
analytical grade. Following are the active pharmaceutical agent and excipients used in
experimental work.
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List of Ingredients
Table No.1: List of Ingredients.
Sr. No. Ingredients Category Manufacturer Company
1. Drug Trandolapril API AurobindoPharma Limited, India
2. Lactose monohydrate NF Diluent DMF
3. Starch (corn starch) NF Diluent Roquette
4. Croscarmellose sodium NF Disintegrant FMC
5. Hypromellose USP Binder Dow Chemical
6. Ferric oxide (Red &Yellow Iron
818802) NF+IH Colorant Sensient
7. Povidone USP Binder BASF
8. Sodium strearylfumarate NF Lubricant Standard Chem
Analysis report of all the raw material was checked and approved raw material was used.
List of Equipments used
List of manufacturing equipments and their qualification status are described in the following
table.
Table No 2: List of equipments.
Sr.No. Manufacturing
stage Equipment’s
Manufactured
By Qualification
1 All applicable stages Weighing Balance
Jay Pan
Qualified Mettler Toledo
A&D co Ltd
2 Sifting Vibratory Sifter Gansons Qualified
3 Wet Granulation Rapid Mixer Granulator
(150L) Saral Qualified
4 Binder Preparation Pneumatic Stirrer Fluidyne Qualified
5 Drying Fluid Bed Dryer
(60kg) Saral Qualified
6 Milling Co-mill R.P.Products Qualified
7 Milling Lifting and tippling device Saral Qualified
8 Blending Piller Blender
(Capacity 150 L) R.P.Products Qualified
9 Compression
Rotary compression machine Kilian Qualified
Combo de-duster and Metal
Detector Kramer Qualified
10 Tablet inspection Tablet Inspection Machine Accura Qualified
Qualified equipments were used for processing and no failure observations noted during
operation of the equipment’s.
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List of Instruments Used
List of Instruments and their qualification status are described in the following table.
Table No 3: List of Instruments.
Sr.No. Instruments Manufactured By Qualification
1. Electronic Balance Mettler Toledo Qualified
2. Moisture analyzer Mettler Toledo Qualified
3. USP Dissolution apparatus Electrolab Qualified
4. Tapped density apparatus Electrolab Qualified
5. Malvern Master Sizer Hydro 2000 S Qualified
6. Hardness tester Schleuniger Qualified
7. pH Meter Thermo scientific Qualified
8. HPLC Shimadzu Qualified
9. Friability test apparatus Electrolab Qualified
10. IR Shimadzu Qualified
11. Water Content by Karl Fisher Metrohn Qualified
12 Melting point apparatus Mettler Toledo Qualified
13 Degasser Electrolab Qualified
14 Angle of repose apparatus Electrolab Qualified
15 Polarimeter Rudolph research analytical Qualified
Qualified instruments were used for processing and no failure observations noted during
operation of the instruments.
List of Primary Packaging Materials
Primary packaging material used in Trandolapril tablets USP described as follows:
Table No. 4: Packaging Components.
Sr. No. Ingredients Function Vendor
1. 60cc ROUND OPAQ HDPE
Bottle Primary packaging Triveni Polymers
2. 033MM CR Closure with Hs123-
35 PRT Kerr Primary packaging BPREX Pharma
3 Silica gel Schet 1g Absorbent Multisorbtechnologies
4 Pharma grade polyster: coil 9G-
Carolina Absorbent
Carolina Adsorbent
Cotton USA
Assessment of critical parameters
Rational for selection of non-critical and critical steps and its process parameters for
validation are given as follows:
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1. Stage :- Dispensing
Equipment: Weighing Balance
Fig. No.1: Weighing Balance for weighing.
Make-Mettler Toledo
Critical Variable- Weight variation
Critical Parameters- Showing weight variation
Rationale- Weighing balance should be calibrated to meet the desired product specification.
2. Stage:- Sifting
Equipment: Vibratory Sifter
Fig. No 2: Vibratory Sifter for sifting.
Make- Gansons
Critical Variable: Particle Size distribution of sifted materials.
Critical Parameters
Particular sieve number
Sieve integrity before and after use.
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Rationale: - To ensure uniform particle size distribution of sifted input material.
3. Stage:- Dry mixing & Wet Granulation
Equipment: Rapid Mixer Granulator
Fig. No. 3: Rapid Mixer Granulator for granulation.
Make- Saral
Capacity- 150 L
Critical Variable:-Speed of Impeller and Chopper
Critical Parameters: -Impeller speed
-Chopper Speed
Rationale: To obtain the homogeneity of granulation process and physical properties of
granules uniformity for compression.
4. Stage: Drying
Equipment: - Fluidized Bed Dyer
Fig. No.4: Fluidized Bed Dyer for drying.
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Make- Saral
Capacity- 60 Kg
Critical Variable: -Temperature
Critical Parameters: -Inlet temperature
: -Outlet temperature
5. Stage:- Milling
Equipment: - Co-mill
Fig. No. 5.5: Co-mill.
Make- Saral
Critical Variable: - Temperature
Critical Parameters: - Speed of Co-Mill Screen used
6. Stage:- Blending
Equipment: - Pillar Blender Bin
Fig. No. 6: Pillar Blender Bin for Blending.
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Make- R. P. Products
Capacity- 150L
Critical Variable: - Blending time (with lubricant)
Blending speed
Critical Parameters
Blending time
Blending speed
Assay
Bulk and Tap density
Sieve Analysis
Blend Uniformity
7. Stage:- compression
Equipment: - Rotary compression machine.
Fig.No. 7: Rotary compression machine.
Make- Kilian
Critical Variable
Force Feeder speed
Compression Machine Speed
Compression force
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Critical Parameters
1) Dissolution
2) Uniformity of dosage unit
3) Friability
4) disintegration
METHOD
Process flow chart
A] INTRA-GRANULAR PART:
INGREDIENTS PROCESS DESCRIPTION TESTS PERFORMED
RAW MATERIAL
QUANTITY
VERIFICATION
[Weighing Balance]
1. Lactose Monohydrate
NF/IH
SIFTING
[Vibratory Sifter- 60 mesh]
1. Drug X SIFTING
[Vibratory Sifter- 40 mesh]
1. Sifted Drug X and
2. Sifted Lactose
Monohydrate NF/IH
in 1:1 proportion
PRE-MIXING (MANUAL)
AND SIFTING (Twice)
[Vibratory Sifter- 60 mesh]
1. Sifted Lactose
Monohydrate NF/IH
and
2. Sifted Drug premix
in 1:1 proportion
PRE-MIXING (MANUAL)
AND SIFTING
[Vibratory Sifter- 60 mesh]
1. Remaining Lactose
Monohydrate
CO-SIFTING
[Vibratory Sifter- 60 mesh]
1. Red Iron Oxide IH
2. Part quantity of
Starch NF
MIXING (MANUAL)
AND SIFTING (Twice)
[Vibratory Sifter- 100 mesh]
1. Remaining quantity
of Starch NF
SIFTING
[Vibratory Sifter- 60 mesh]
1. Hypromellose USP and
2. Croscarmellose Sodium
SIFTING
[Vibratory Sifter- 40 mesh]
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INGREDIENTS PROCESS DESCRIPTION TESTS PERFORMED
NF
1. Povidone USP and
2. Purified water USP
BINDER PREPARATION
[S.S. Container and Stirrer]
Sifted (Order-wise)
1. Hypromellose USP
and Croscarmellose
Sodium NF (Half
quantity)
2. Drug X-Lactose
Monohydrate
powder mix
3. Color-Starch
Concentrate
4. Starch NF
5. Hypromellose USP
and Croscarmellose
Sodium NF
(Remaining
quantity)
DRY MIXING
[Rapid Mixer Granulator- 150
L]
[Mixing time- 15:00 Minutes:
Seconds]
[Impeller: Slow, Chopper: Off]
1.Blend Uniformity
1. Binder Solution
2. Purified Water USP
WET GRANULATION
[Rapid Mixer Granulator- 150
L]
Binder/P. Water Addition-
Impeller: Slow, Chopper: Slow
Wet mixing-
Impeller: Fast, Chopper: Fast
DRYING
[Fluid Bed Dryer - 60 kg]
Air Drying Time: 05 Minutes
Inlet Air Temperature: 60°C ±
5°C
(55 - 65°C)
1. Loss on Drying (%
w/w)
1. Dried Granules
SIFTING OF DRIED
GRANULES
[Vibratory Sifter- 30 mesh]
1. Oversized Granules
MILLING AND SIFTING
OF
OVERSIZE GRANULES
[Co-Mill- 1.0 mm S. S.
Screen]
[Vibratory Sifter- 30 mesh S.S.
Sieve]
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INGREDIENTS PROCESS DESCRIPTION TESTS PERFORMED
Milling Speed: Slow/Fast
[Milling and sifting to be done
till all materials passed
through 30 mesh S.S. Sieve]
B]EXTRA
GRANULAR PART:
1. Sodium
StearylFumarate
SIFTING OF EXTRA-
GRANULAR MATERIAL
[Vibratory Sifter- 60 mesh]
1. Sifted Sodium
StearylFumarate
2. Approximately 2 kg
of sized granules
MIXING (MANUAL BY
TURNING TWICE) AND
SIFTING
[Vibratory Sifter- 30 mesh]
1. Sized Granules
2. Sodium
StearylFumarate and
Sized granules pre-
mix
LUBRICATION
[Pillar blender- 150 L]
[Mixing time- 05:00
Minutes: Seconds]
[Blender Speed- 05 rpm]
1. Description
2. Composite Blend
Assay
3. Blend Uniformity
4. Bulk density
5. Tapped Density
6. Compressibility index
7. Hausner’s ratio
8. Particle
size distribution
9. Angle of repose
COMPRESSION [Tablet Compression Machine,
Deduster and Metal Detector]
[Punch Specification: 6.0 mm
round, standard concave
punches, UP "H01" and LP
“L” and “U” on either side of
scoreline]
1. Description
2. Weight of 20 tablets
3. Uniformity of weight
4. Thickness
5. Tablets Breaking force
6. Disintegration Time
7. Friability
8. Dissolution
9. Uniformity of dosage
unit (By content
Uniformity)
Complete analysis as
per finished product
release specification
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Process Description
1.0 Dispensing
1.1 The required quantities of ingredients were dispensed as per raw material requisition
sheet.
1.2 The weights and Q.C batch numbers of dispensed ingredients were checked and verified.
2.0 Sifting
2.1 Dispensed quantity of Lactose Monohydrate NF was sifted through 60 mesh S.S. sieve
using vibratory sifter.
2.2 Dispensed quantity of Drug X was sifted through 40 mesh S.S. sieve by manually.
2.3 Step 2.2 sifted Drug X was mixed together with sifted Lactose Monohydrate of step 2.1
geometrically in 1:1 proportion.
2.4 Step 2.3 mixed material was sifted through 60 mesh S.S sieve manually.
2.5 Step 2.4 material was again sifted through 60 mesh S.S. sieve manually.
2.6 Lactose Monohydrate from step 2.1 & drug premix were mixed geometrically in 1:1
proportion in polybag and sifted through 60 mesh S.S. sieve manually.
2.7 Step 2.6 drug premix was sifted with remaining quantity of step 2.1 Lactose Monohydrate
through 60 mesh S.S sieve manually.
2.8 Ferric Oxide NF+IH (Red Iron 800416) was mixed with total Qty of Starch NF and sifted
twice through 100 mesh S.S. sieve.
2.9 Remaining Starch NF was sifted through 60 mesh S.S. sieve on vibratory sifter.
2.10 Hypromellose IP was sifted through 40 mesh S.S. sieve on vibratory sifter.
2.11 Croscarmellose Sodium NF was sifted through 40 mesh S.S. sieve on vibratory sifter.
3.0 Binder Preparation
3.1Povidone USP was dissolved in purified water using stirrer to get approximately 20%
W/W solution in S.S. container.
3.2 Continued stirring till clear solution is formed.
Total Stirring Time: 16 Minutes
4.0 Wet Granulation
4.1 Dry mixing
4.1.1 Sifted material of step 2.10 and step 2.11 were loaded into RMG approximately half
Qty. followed by Drug X – Lactose monohydrate powder mix of step 2.7, colour concentrate
of step 2.8, sifted remaining Starch of step 2.9 and remaining Qty. of step 2.10 & 2.11.
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4.1.2 The content of RMG were mixed for 15 minutes at agitator slow speed and chopper off.
4.2 Binder addition
4.2.1 Added step 3.2 Povidone solution into RMG content for 2 min. with slow agitator &
slow chopper.
Impeller Ampere – 12.6 A (slow)
Chopper Ampere – 2.2 A (slow)
4.3 Wet mixing
4.3.1The content of RMG was mixed by addition of purified water for 1 min.
Impeller Ampere – 8.6 A (fast)
Chopper Ampere – 2.2 A (fast)
4.3.2 Continued the granulation for 1 min.
Impeller Ampere – 8.3 A (fast)
Chopper Ampere – 2.2 A (fast)
4.3.3 After satisfactory granulation content of RMG were discharged with impeller and
chopper at fast speed in FBD bowl.
5.0 Drying
5.1 The content of FBD bowl were air dried under FBD with following parameters:
i) Air drying time - 5 minutes
ii) Inlet Temp. – 26.7⁰C
iii) Outlet Temp. – 20.5⁰C
iv) FCD – 30%
5.2 Further material in FBD bowl was dried with steam drying for 10 minutes.
i) Inlet Temp. – 58.8⁰C
ii) Outlet Temp. – 28.4⁰C
iii) FCD – 30 (8 min) ; 25 (2 min)
iv) LOD - 4.07%
FBD was stopped and LOD was checked which was found more than the specified limit (i.e.
Between 2.0-3.5% at 105⁰C), hence again drying was continued.
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5.3 Steam drying was continued for 3 minutes.
i) Inlet Temp. – 58.8⁰C
ii) Outlet Temp. – 37.5⁰C
iii) FCD – 25%
iv) LOD - 2.13% (within limit; hence drying stopped)
Total air drying time – 05 min
Total steam drying time – 13 min
LOD: Top – 2.02% ; Middle – 2.37% ; Bottom – 2.45%
6.0 Sifting of dried granules
6.1 Dried granules of step 5.3 were sifted through 30 mesh S.S sieve fitted on Vibratory
Sifter and collected in double polybag lined IPC as under size granules.
Quantity of oversize granules- 6.96 kg.
Quantity of undersize granules- 22.24 kg.
7.0 Milling
7.1 Above oversize material was milled through 1.0 mm S.S. screen fitted on co-mill at
milling speed of 25 Hz and collected in double polythene bag lined container. This milled
material was then sifted through 30 mesh S.S. sieve and undersize and oversize materials
were collected separately in double polythene bag lined containers.
Total Weight of Oversize Granules- 1.30 kg
7.2 Above oversize material was again milled through 1.0 mm S.S. screen fitted on co-mill at
milling speed of 60 Hz and collected in double polythene bag lined container. This milled
material was then sifted through 30 mesh S.S. sieve and undersize and oversize materials
were collected separately in double polythene bag lined containers.
Total Weight of Oversize Granules- 0.92 kg
7.3 Above oversize material was again milled through 1.0 mm S.S. screen fitted on co-mill at
milling speed of 60 Hz and collected in double polythene bag lined container. This milled
material was then sifted through 30 mesh S.S. sieve and undersize and oversize materials
were collected separately in double polythene bag lined containers.
Total Weight of Oversize Granules- 0.66 kg
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7.4 Above oversize material was again milled through 1.0 mm S.S. screen fitted on co-mill at
milling speed of 60 Hz and collected in double polythene bag lined container. This milled
material was then sifted through 30 mesh S.S. sieve and undersize and oversize materials
were collected separately in double polythene bag lined containers.
Total Weight of Oversize Granules- 0.30 kg
7.5 Above oversize material was again milled through 1.0 mm S.S. screen fitted on co-mill at
milling speed of 60 Hz and collected in double polythene bag lined container. This milled
material was then sifted through 30 mesh S.S. sieve and undersize and oversize materials
were collected separately in double polythene bag lined containers.
Total Weight of Oversize Granules- 0.09 kg
7.6 Above oversize material was then passed by manually pressing through 30 mesh S.S.
sieve fitted on vibratory sifter.
7.7 All undersize granules were loaded in 150 L capacity pillar blender bin.
8.0 Lubricant sifting
8.1 Dispensed quantity of Sodium Stearyl Fumarate was sifted through 60 mesh S.S. sieve
using vibratory sifter and collected in a double polythene bag lined container.
8.2 Approximately 2 kg undersize granules and sifted Sodium Stearyl Fumarate were mixed
together manually in polybag by turning twice.
8.3 Above mixed material was sifted through 30 mesh S.S. sieve using vibratory sifter,
collected in a double polythene bag lined container and added to blender bin of step 7.7.
9.0 Blending
9.1 The contents in blender bin were mixed for 05 minutes at 5 rpm using pillar blender.
Sampling was performed as per sampling plan provided in sampling protocol (Die used-
0.3 mL round shaped Die).
9.2 Unloading of Lubricated Blend into in-process container.
10.0 Compression
10.1 Above lubricated blend was compressed using double rotatory compression machine.
At initially stage of compression sticking was observed on upper surface of tablets,
subsequently punches were cleaned, then compression was continued and further no
sticking was appeared on tablet surface. During compression in-process tests were
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performed at minimum machine speed, maximum machine speed and also at start, middle
and end of compression run. Tablet parameters at these stages were checked for in-
process tests and found complying with the specified limits.
Steps Involved in Process Validation of Trandolapril Tablets[23]
1) Sifting (correct Mesh Size),
2) Mixing and Blending (dry mixing, binder addition, wet mixing, in-process control
checks etc.),
3) Granulation (Binder addition, Mixing time) done using Rapid Mixer Granulator and
samples were collected from 10 sampling locations as given in following diagram.
Figure No. Schematic Diagram of RMG.
4) Drying (LOD), by using Fluid Bed Dryer and samples for in process control checks were
collected from 7 different locations as shown in following Diagram.
Figure No. Schematic Diagram of Fluid Bed Dryer
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5) Sizing and Milling (Mesh Size), done using Co-Mill.
6) Lubrication (Blending Time, Blending Speed), performed using Bin Blender and samples
were collected from 10 different locations as shown in following diagram.
Figure No. Schematic Diagram of Bin Blender.
7) Compression (Hardness, Speed, in process checks like Appearance of tablet, group
weight, Average weight, Uniformity of weight, Thickness, Hardness, Length, width, and
Friability etc), done using Rotary compression machine. Collected 54 tablets from each
interval; make a composite sample from initial, middle, and end. For the study 20 tablets
were considered as whole composite.
Table No. 9: Acceptance criteria during compression.
Test Acceptance criteria
Appearance Pink, round, biconvex, uncoated tablets
Group weight -----
Uniformity of weight ± 5% of theoretical average weight
(95.000 to 105.000 mg)
Average weight 2.000 g ± 3% (1.940 to 2.060 g)
Thickness 3.10 ± 0.20 mm (2.90 mm to 3.30 mm)
Hardness 60 ± 20 N (40 N to 80 N)
Friability NMT 0.8%
Disintegration Time NMT 15:00
Assay 95 to 105%
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Different Defects Related To Tablets
Tablets were checked for following defects after compression:
Capping, Lamination, Chipping, Cracking, Sticking, Picking, Binding, Mottling, Double
impression, Bridging, Erosion, Twinning, Peeling, Frostin, Orange peel etc.
Pack Profile
The compressed tablets were packed in the container as follows:
33mm-66cc WM heavy weight round HDPE bottle containing 100tablets with and CR
closure (33-400) PP with induction heat sealed HS123 printed liner.
Equipment Evaluation
All the equipments which were used in the manufacturing of Trandolapril tablets evaluated as
per requirement and found satisfactory.
The equipments are as follows:
Mixer/granulator, Blender, Dryer, Mills etc.
RESULT AND DISCUSSION
1. Results for Sifting
Table: Sifting Results.
Batch No. Integrity of Sieve Before Integrity of Sieve After
A1 Complies Complies
A2 Complies Complies
A3 Complies Complies
Trandolapril, Hypromellose IP and Croscarmellose Sodium NF was sifted through sieve #40
on vibrosifter. Lactose and Sodium Stearyl Fumarate sifted through sieve #60. Ferric Oxide
NF+IH and starch through sieve #100.
Integrity of sieve before use and Integrity of sieve after use was checked and found
complying with specifications.
2. Results for Dry mixing
Table: Blending mixing time.
Assessment Parameters Observation
Mixing Time 15min
Speed of RMG Slow
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The raw materials were mixed for 15minutes in RMG at slow speed with knife in forward
direction.
Table: Blend Uniformity Results.
Sample % Assay (Acceptance Criteria: 90% to 110% RSD : NMT 5%)
(Time :15 min)
B.No. A1 B.No. A2 B.No. A3
T1 99.4 97.1 95.1
T2 104.8 99.0 101.8
M1 99.5 100.6 95.2
M2 105.4 95.9 96.3
B1 103.6 93.3 91.9
B2 104.7 98.1 96.4
Min. 99.4 93.3 91.9
Max. 105.4 100.6 101.8
Mean % 102.9 97.3 96.1
RSD % 2.8 2.6 3.1
6 locational samples have been collected by using sampling rod and tested for blend
uniformity by using HPLC.
Batch No A1: Minimum value was 99.4%, maximum value was 105.4%, mean value was
102.9 and RSD was found to be 2.8.
Batch No. A2: Minimum value was 93.3%, maximum value was 100.6%, mean value was
97.3 and RSD was found to be 2.6.
Batch No. A3: Minimum value was 91.9%, maximum value was 101.8%, mean value was
96.1 and RSD was found to be 3.1.
Process parameters comply with the requirements as given in the protocol.
All the results of Blend uniformity were found within the acceptance criteria as per approved
specifications.
Table: Bulk Density Results.
Acceptance
criteria
Batch
No.
Sample
size
Untapped bulk
density
Tapped bulk
density
To record A1 30 g 0.63 0.71
To record A2 30 g 0.59 0.72
To record A3 30 g 0.63 0.71
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One 30g composite sample have been collected and tested for bulk density (Tapped &
Untapped) by using bulk density tester.
Batch No. A1: The results for untapped bulk density were found to be 0.63 and for tapped
bulk density 0.71.
Batch No. A2: The results for untapped bulk density were found to be 0.59 and for tapped
bulk density 0.72.
Batch No. A3: The results for untapped bulk density were found to be 0.63 and for tapped
bulk density 0.71.
Process parameters comply with the requirements as per given in the protocol.
3. Results for Drying
Table: LOD Results.
Sample Acceptance
criteria
Weight
reuired (g)
LOD in %w/w
B.No.
A1 B.No.
A2
B.No.
A3
T1
2.0– 3.5 % w/w 2 – 5 g
2.44 2.59 2.53
T2 2.28 2.81 2.59
M1 2.43 2.57 2.83
M2 2.44 2.82 2.60
M3 2.39 2.68 2.42
B1 2.42 2.65 2.63
B2 2.40 2.75 2.55
Average 2.4 2.69 2.59
Granulated wet mass were transferred to FBD from RMG and dried for 10 minutes. 7
locational samples 2–5gm were collected as per sampling locations by using sampling rod
and tested for LOD by putting the sample in LOD bottles and dried it in Oven for specified
time at specified temperature.
Batch No. A1: From the top 2 portion LOD results were found to be 2.44% and 2.28%, From
middle portion 2.39-2.44% and from bottom portion 2.42% and 2.43%. Average value for
LOD was found to be 2.4%.
Batch No. A2: From the top 2 portion LOD results were found to be 2.59% and 2.81%, From
middle portion 2.57-2.82% and from bottom portion 2.65% and 2.75%. Average value for
LOD was found to be 2.69%.
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Batch No. A3: From the top 2 portion LOD results were found to be 2.53% and 2.59%, From
middle portion 2.60-2.83% and from bottom portion 2.55% and 2.63%. Average value for
LOD was found to be 2.59%.
Process parameters comply with the requirements as given in the protocol. All the results of
LOD were found within the acceptance criteria as per approved specifications.
4. Results for Milling
Table: PSD Results.
Sieve size Acceptance criteria % w/w Retention
B.No. A1 B.No. A2 B.No. A3
20#
To record
0.0 0.0 0.0
60# 32.3 31.0 33
80# 49 46 49
120# 67 62 66
200# 81 79 82
% w/w passed through
200# To record 16 17 18
Particle size of the milled granules were checked by passing it through various sieves i.e. 20#,
60#, 80#, 100#,120# &200# by using sieve shaker.
Batch No. A1: PSD results are as follows:
From the sieve size 20# 0.0 % sample retention were observed, from sieve size 60# 33%
sample retention were observed, from sieve size 80#.49% sample retention were observed,
from sieve size 120# 67% sample retention was observed, from sieve size 200# 82% sample
retention were observed and 16% sample was below sieve size 200#.
Batch No. A2: PSD results are as follows:
From the sieve size 20# 0.0 % sample retention were observed, from sieve size 60# 31%
sample retention were observed, from sieve size 80# 46% sample retention were observed,
from sieve size 120# 62% sample retention was observed, from sieve size 200# 79% sample
retention were observed and 17% sample was passed through sieve size 200#.
Batch No. A3: PSD results are as follows:
From the sieve size 20# 0.0 % sample retention were observed, from sieve size 60# 33%
sample retention were observed, from sieve size 80# 49% sample retention were observed,
from sieve size 120# 66% sample retention was observed, from sieve size 200# 82% sample
retention were observed and 18% sample was passed through sieve size 200#.
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Process parameters comply with the requirements as given in the protocol.
5. Results for Lubrication
Table: Blending mixing time.
Assessment Parameters Observation
Mixing Time 5 min
Speed of Bin blender 5rpm
Milled granules were transferred to Bin blender and mixed for 15 minutes at slow speed after
that Lubricant was added and again mixed for 5 minutes at 5rpm speed.
Table: Blend Uniformity Results.
Sample % Assay (Acceptance Criteria: 90% to 110% RSD : NMT 5%)
(Time : 5 min)
B.No. A1 B.No. A2 B.No. A3
T1 103.0 98.7 98.4
T2 99.9 98.9 100.0
T3 100.3 99.1 98.4
T4 99.5 104.3 97.9
M1 100.1 98.5 98.3
M2 104.3 99.0 101.1
M3 103.0 99.6 98.1
B1 107.5 105.4 100.5
B2 97.6 100.7 100.9
B3 101.2 98.8 97.8
Min. 97.6 98.5 97.8
Max. 107.5 105.4 101.1
Mean% 101.6 100.3 99.1
RSD% 2.9 2.5 1.3
10 locational samples have been collected by using sampling rod and tested for blend
uniformity by using HPLC.
Batch No. A1: From the top portion results were found between 99.5-103.0%, from middle
portion 100.1-104.3% and from bottom portion 97.6-107.5%, minimum value was 97.6%,
maximum value was 107.5%, mean value was 101.6 and RSD was found to be 2.9.
Batch No. A2: From the top portion results were found between 98.7-104.3%, from middle
portion 98.5-99.6% and from bottom portion 98.8-105.4%, minimum value was 98.5%,
maximum value was 105.4%, mean value was 100.3 and RSD was found to be 2.5.
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Batch No. A3: From the top portion results were found between 97.9-100.0%, from middle
portion 98.1-101.1% and from bottom portion 97.8-100.9%, minimum value was 97.8%,
maximum value was 101.1%, mean value was 99.1 and RSD was found to be 1.3.
Process parameters comply with the requirements as given in the protocol.
All the results of Blend uniformity were found within the acceptance criteria as per approved
specifications.
Table: Assay Results of Lubricated granules.
Acceptance Criteria: 95.0 % - 105.0%
B. No. A1 B. No. A2 B. No. A3
98.0 % 98.9 % 97.6 %
Lubricated granules were withdrawn from each batch and tested for Assay by using HPLC.
The assay result for batch No A1, A2, A3 was found to be 98.0%, 98.9%, 97.6% respectively.
All the results were found within specification limit.
6. Compression
A. Hardness Variation
Table: Results of hardness variation (Batch- A1, A2, A3).
Test Acceptance Criteria --- Low
Hardness
High
Hardness
Appearance
Pink, round, biconvex,
uncoated tablets with
“L”& “U” on either side
of breakline on one side&
“H01”. on the other side.
--- Complies Complies
weight of 20
tablets
2.000g ± 3.0 %
(1.940 – 2.060 g)
Min. 2.000 2.003
Max. 2.015 2.005
Uniformity of
Weight (mg)
±5% of theoretical
average weight
(95.00-105.00mg)
--- 0.1008 0.1005
D. T. (min: sec.) NMT 15:00 --- 2.10 3.40
Thickness 3.10mm ± 0.20mm
(2.90-3.30mm)
Min. 3.30 3.12
Max. 3.36 3.15
Avg. 3.33 3.14
Hardness 60±20N
(40 – 80 N)
Min 29 80
Max. 40 99
Avg. 35 91
Friability NMT 0.8 % w/w -- 0.092 0.076
Assay 95% to 105% --- 96 98
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Lubricated granules were compressed by using rotary compression machine. During
compression cycle samples were collected at min/max hardness.
For Low Hardness: Compression results obtained are as follows:
1. weight of 20 tablets:(acceptance criteria- (1.940 – 2.060 g): 20 tablets were accurately
weighed by using calibrated balance and the results were found to be min. 2.000g and
max. 2.015g.
2. Uniformity of Weight (mg) (acceptance criteria- 95.00-105.00mg): All tablets have been
weighed accurately by using calibrated balance and the average weight were calculated.
The results were found to be 0.1008.
3. Disintegration Time: (NMT 15:00): Disintegration time was determined by the
disintegration apparatus and results were found to be 02:10.
4. Thickness (acceptance criteria- 2.90-3.30mm):
Thickness of 10 tablets was checked by using vernier caliper and the results found to be
min. 3.30mm, max. 3.36mm and avg. 3.33mm.
5. Hardness (acceptance criteria- 40 – 80 N):
Hardness of 10 tablets were tested using hardness tester and the results found to be at
min. hardness min. 29N, max. 40N, avg. 35N.
6. Friability (acceptance criteria- NMT 0.8 % w/w): Friability of tablets were checked by
using friability tester and the results found to be 0.092.
7. Assay (acceptance criteria- 95% to 105%): The assay of compressed tablets were carried
out by using HPLC and result was found to be 96%.
For High Hardness: Compression results obtained are as follows:
1. Weight of 20 tablets :(acceptance criteria- (1.940 – 2.060 g): 20 tablets were accurately
weighed by using calibrated balance and the results were found to be min. 2.003 and max.
2.005.
2. Uniformity of Weight (mg) (acceptance criteria- 95.00-105.00mg): All tablets have been
weighed accurately by using calibrated balance and the average weight were calculated.
The results found to be 0.1005.
3. Disintegration Time: (NMT 15:00): Disintegration time was determined by the
disintegration apparatus and results were found to be 03:40.
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4. Thickness (acceptance criteria- 2.90-3.30mm): Thickness of 10 tablets was checked by
using vernier caliper and the results found to be min. 3.12mm, max. 3.15mm and avg.
3.14mm.
5. Hardness (acceptance criteria- 40 – 80 N): Hardness of 10 tablets were tested using
hardness tester and the results found to be at min. hardness min. 80N, max. 99N, avg.
91N.
6. Friability (acceptance criteria- NMT 0.8 % w/w): Friability of tablets were checked by
using friability tester and the result found, to be 0.076.
7. Assay (acceptance criteria- 95% to 105%): The assay of compressed tablets was carried
out by using HPLC and the result found to be 98%.
The data of physical & analytical parameters carried on samples collected during low
hardness & high hardness for all three validation batches are found within the limits of
acceptance criteria.
B. Speed variation
Table 7.12 Results of Speed variation (Batch- 01, 02, 03).
Test Acceptance Criteria --- Low
Speed
High
Speed
Appearance
Pink, round, biconvex, uncoated
tablets with “L”& “U” on either side
of breakline on one side& “H01”. on
the other side.
--- Complies Complies
weight of 20 tablets 2.000g ± 3.0 %
(1.940 – 2.060 g)
Min. 1.990 2.004
Max. 1.992 2.009
Uniformity of
Weight (mg)
±5% of theoretical average weight
(95.00-105.00mg) --- 0.09941 0.10018
D. T. (min: sec.) NMT 15:00 --- 0.238 0.242
Thickness 3.10mm ± 0.20mm
(2.90-3.30mm)
Min. 3.08 3.12
Max. 3.21 3.23
Avg. 3.16 3.19
Hardness 60±20N
(40 – 80 N)
Min 47 55
Max. 78 76
Avg. 64 66
Friability NMT 0.8 % w/w -- 0.031 0.031
Assay 95% to 105% --- 97 98
Lubricated granules were compressed by using rotary compression machine. During
compression cycle samples were collected at min/max speed.
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For Low Speed: Compression results obtained are as follows:
1. Weight of 20 tablets (acceptance criteria- 1.940 – 2.060 g): 20 tablets were accurately
weighed by using calibrated balance and the results were found to be min. 1.990g and
max. 1.992g.
2. Uniformity of Weight (mg) (acceptance criteria- 95.00-105.00mg): All tablets have been
weighed accurately by using calibrated balance and the average weight was calculated.
The results found to be 0.09941.
3. Disintegration Time (acceptance criteria- NMT 15:00): Disintegration time was
determined by the disintegration apparatus and results were found to be 0.238
4. Thickness (acceptance criteria- 2.90-3.30mm): Thickness of 10 tablets was checked by
using vernier caliper and the results found to be min. 3.08mm, max. 3.21mm and avg.
3.16mm.
5. Hardness (acceptance criteria- 40 – 80 N): Hardness of 10 tablets were tested using
hardness tester and the results found to be at min. hardness min. 47N, max. 78N, avg.
64N.
6. Friability (acceptance criteria- NMT 0.8 % w/w): Friability of tablets were checked by
using friability tester and the result found to be 0.031.
7. Assay (acceptance criteria- 95% to 105%): The assay of compressed tablets was carried
out by using HPLC and the result found to be 98%.
For High Speed: Compression results obtained are as follows:
1. Weight of 20 tablets (acceptance criteria- 1.940 – 2.060 g): 20 tablets were accurately
weighed by using calibrated balance and the results were found to be min. 2.004g and
max. 2.009g.
2. Uniformity of Weight (mg) (acceptance criteria- 95.00-105.00mg): All tablets have been
weighed accurately by using calibrated balance and the average weight was calculated.
The results found to be 0.10018.
3. Disintegration Time (acceptance criteria- NMT 15:00): Disintegration time was
determined by the disintegration apparatus and results were found to be 0.242.
4. Thickness (acceptance criteria- 2.90-3.30mm): Thickness of 10 tablets was checked by
using vernier caliper and the results found to be min. 3.12mm, max. 3.23mm and avg.
3.19mm.
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5. Hardness (acceptance criteria- 40 – 80 N): Hardness of 10 tablets were tested using
hardness tester and the results found to be at min. hardness min. 55N, max. 76N, avg.
66N.
6. Friability (acceptance criteria- NMT 0.8 % w/w): Friability of tablets were checked by
using friability tester and the result found to be 0.031.
7. Assay (acceptance criteria- 95% to 105%): The assay of compressed tablets was carried
out by using HPLC and the result found to be 97%.
The data of physical & analytical parameters carried on samples collected during low speed
& high speed for all three validation batches are found within the limits of acceptance
criteria.
C. At optimum condition
Optimum condition means the speed of the machine and the hardness of the machine were
kept at optimum level, i.e. speed – 20rpm, hardness – 80-130N
Table: Results of compression parameters at optimum condition (Batch- 01, 02, 03).
Test Acceptance Criteria --- Initial Middle End
Appearance
Pink, round, biconvex, uncoated tablets
with “L”& “U” on either side of breakline
on one side& “H01”. on the other side.
--- Complies Complies Complies
weight of 20 tablets 2.000g ± 3.0 %
(1.940 – 2.060 g) 1.9950 2.0050 1.9970
Uniformity of
Weight (mg)
±5% of theoretical average weight (95.00-
105.00mg) --- 0.10025 0.10050 0.10035
D. T. (min: sec.) NMT 15:00 --- 02:40 02:35 02:30
Thickness 3.10mm ± 0.20mm
(2.90-3.30mm)
Min. 3.17 3.17 3.17
Max. 3.20 3.22 3.20
Avg. 3.19 3.20 3.19
Hardness 60±20N
(40 – 80 N)
Min 54 57 60
Max. 71 69 69
Avg. 63 63 64
Friability NMT 0.8 % w/w -- 0.077 0.077 0.123
Assay 95% to 105% --- 98 98.5 97
Lubricated granules were compressed by using rotary compression machine. During
compression cycle samples were collected at Initial, Middle and End stage of compression.
At initial stage: Compression results obtained are as follows:
1. Weight of 20 tablets test (acceptance criteria- 1.940 – 2.060 g)): 20 tablets were
accurately weighed by using calibrated balance and the results were found to be 1.9950g.
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2. Uniformity of weight (acceptance criteria- 95-105 mg): All tablets have been weighed
accurately by using calibrated balance and the average weight were calculated. The result
found to be 0.10025.
3. Thickness (acceptance criteria- 2.90 mm-3.30 mm): Thickness of 10 tablets were
checked by using vernier caliper and the results found to be min. 3.17mm, max. 3.20mm
and avg. 3.19mm.
4. Disintegration Time (acceptance criteria- NMT 15:00): Disintegration time was
determined by the disintegration apparatus and results were found to be 2.40.
5. Hardness (acceptance criteria- 40N-80N): Hardness of 10 tablets were tested using
hardness tester and the results found to be min. 54N, max. 71N and avg. 63N.
6. Friability (acceptance criteria- NMT 0.8 % w/w): Friability of tablets were checked by
using friability tester and the results found to be 0.077.
7. Assay (acceptance criteria- 95% to 105%): The assay of compressed tablets were carried
out by using HPLC and the result found to be 98%.
At middle stage: Compression results obtained are as follows:
1. Weight of 20 tablets test (acceptance criteria- 1.940 – 2.060 g)): 20 tablets were
accurately weighed by using calibrated balance and the results were found to be 2.0050g.
2. Uniformity of weight (acceptance criteria- 95-105 mg): All tablets have been weighed
accurately by using calibrated balance and the average weight were calculated. The result
found to be 0.10050.
3. Thickness (acceptance criteria- 2.90 mm-3.30 mm): Thickness of 10 tablets were
checked by using vernier caliper and the results found to be min. 3.17mm, max. 3.20mm
and avg. 3.19mm.
4. Disintegration Time (acceptance criteria- NMT 15:00): Disintegration time was
determined by the disintegration apparatus and results were found to be 2.35.
5. Hardness (acceptance criteria- 40N-80N): Hardness of 10 tablets were tested using
hardness tester and the results found to be min. 57N, max. 69N and avg. 63N.
6. Friability (acceptance criteria- NMT 0.8% w/w): Friability of tablets were checked by
using friability tester and the results found to be 0.077.
7. Assay (acceptance criteria- 95% to 105%): The assay of compressed tablets were carried
out by using HPLC and the result found to be 98.5%.
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At end stage: Compression results obtained are as follows:
1. Weight of 20 tablets test (acceptance criteria- 1.940 – 2.060 g)): 20 tablets were
accurately weighed by using calibrated balance and the results were found to be 1.9970g.
2. Uniformity of weight (acceptance criteria- 95-105 mg): All tablets have been weighed
accurately by using calibrated balance and the average weight were calculated. The result
found to be 0.10035.
3. Thickness (acceptance criteria- 2.90 mm-3.30 mm): Thickness of 10 tablets were
checked by using vernier caliper and the results found to be min. 3.17mm, max. 3.20mm
and avg. 3.19mm.
4. Disintegration Time (acceptance criteria- NMT 15:00): Disintegration time was
determined by the disintegration apparatus and results were found to be 2.30.
5. Hardness (acceptance criteria- 40N-80N): Hardness of 10 tablets were tested using
hardness tester and the results found to be min. 60N, max. 69N and avg. 64N.
6. Friability (acceptance criteria- NMT 0.8 % w/w): Friability of tablets were checked by
using friability tester and the results found to be 0.123.
7. Assay (acceptance criteria- 95% to 105%): The assay of compressed tablets were carried
out by using HPLC and the result found to be 97%.
The data of physical & analytical parameters carried on samples collected during initial,
middle and end stage of compression for all three validation batches are found within the
limits of acceptance criteria.
Evaluation of Finished Product
Table: Analytical Results of Finished Product.
Tests Acceptance criteria Observation
A1 A2 A3
Description
Pink, round, biconvex,
uncoated tablets with “L”& “U”
on either side of break line on
one side& “H01”. on the other
side.
Complies Complies Complies
Identification by
HPLC
The retention time of the major
peak in the chromatogram of
the test preparation corresponds
to that of the standard
preparation, as obtained in
assay.
Complies Complies Complies
weight of 20
tablets
2.000g ± 3.0 %
(1.940 – 2.060 g) 1.995 2.005 2.003
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Uniformity of
Dosage Units
(by weight
variation)
Acceptance Value Not more
than 15. 8.8 8.8 8.8
Hardness 60±20N
(40 – 80 N)
Min: 56 Min: 56 Min: 56
Max: 70 Max: 72 Max: 68
Friability NMT 0.8 % 0.107 0.077 0.092
Assay 95-105 % 99 97 98.5
Water content by
KF(%W/W) NMT 7.50 6.45 6.55 6.50
Dissolution
NLT 80% Q of the labelled
amount of Trandolapril is
dissolved in 45 min.
Min: 96 Min: 97 Min: 96
Max: 99 Max: 95 Max: 98
Avg.: 98 Avg.: 96 Avg.: 97
Batch A1
1. Weight of 20 tablets test (acceptance criteria- 1.940 – 2.060 g)): 20 tablets were
accurately weighed by using calibrated balance and the results were found to be 1.995g.
2. Uniformity of dosage unit (acceptance criteria- Acceptance Value NMT 15): All tablets
have been weighed accurately by using calibrated balance and the average weight were
calculated. The result found to be 8.8.
3. Hardness (acceptance criteria- 40N-80N): Hardness of 10 tablets were tested using
hardness tester and the results found to be min. 56N and max. 70N.
4. Friability (acceptance criteria- NMT 0.8 % w/w): Friability of tablets were checked by
using friability tester and the results found to be 0.077
5. Assay (acceptance criteria- 95% to 105%): The assay of compressed tablets were carried
out by using HPLC and the result found to be 97%.
6. Water content by KF(%W/W) (acceptance criteria- NMT 7.50): The water content was
found to be 6.45%.
7. Dissolution (acceptance criteria- NLT 80% Q of the labelled amount of Trandolapril is
dissolved in 45 min.): Dissolution was carried out and results were found to be min. 96%,
max. 99% and avg. 98%.
Batch A2
1. Weight of 20 tablets test (acceptance criteria- 1.940 – 2.060 g)): 20 tablets were
accurately weighed by using calibrated balance and the results were found to be 2.005g.
2. Uniformity of dosage unit (acceptance criteria- Acceptance Value NMT 15): All tablets
have been weighed accurately by using calibrated balance and the average weight were
calculated. The result found to be 8.8.
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3. Hardness (acceptance criteria- 40N-80N): Hardness of 10 tablets were tested using
hardness tester and the results found to be min. 56N and max. 72N.
4. Friability (acceptance criteria- NMT 0.8 % w/w): Friability of tablets were checked by
using friability tester and the results found to be 0.107
5. Assay (acceptance criteria- 95% to 105%): The assay of compressed tablets were carried
out by using HPLC and the result found to be 99%.
6. Water content by KF(%W/W) (acceptance criteria- NMT 7.50): The water content was
found to be 6.55%.
7. Dissolution (acceptance criteria- NLT 80% Q of the labelled amount of Trandolapril is
dissolved in 45 min.): Dissolution was carried out and results were found to be min. 97%,
max. 95% and avg. 96%.
Batch A3
1. Weight of 20 tablets test (acceptance criteria- 1.940 – 2.060 g)): 20 tablets were
accurately weighed by using calibrated balance and the results were found to be 2.003g.
2. Uniformity of dosage unit (acceptance criteria- Acceptance Value NMT 15): All tablets
have been weighed accurately by using calibrated balance and the average weight were
calculated. The result found to be 8.8.
3. Hardness (acceptance criteria- 40N-80N): Hardness of 10 tablets were tested using
hardness tester and the results found to be min. 56N and max. 68N.
4. Friability (acceptance criteria- NMT 0.8 % w/w): Friability of tablets were checked by
using friability tester and the results found to be 0.092.
5. Assay (acceptance criteria- 95% to 105%): The assay of compressed tablets was carried
out by using HPLC and the result found to be 98.5%.
6. Water content by KF(%W/W) (acceptance criteria- NMT 7.50): The water content was
found to be 6.50%.
7. Dissolution (acceptance criteria- NLT 80% Q of the labelled amount of Trandolapril is
dissolved in 45 min.): Dissolution was carried out and results were found to be min. 96%,
max. 98% and avg. 97%.
Visual Inspection Test
Tablets were checked for following defects after compression
Capping, Lamination, Chipping, Cracking, Sticking, Picking, Binding, Mottling, Double
impression, Bridging, Erosion, Twinning, Peeling, Frosting, Orange peel No defect were
observed on the tablets after the compression.
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Chaudhari et al. World Journal of Pharmaceutical Research
Packing
Result of Debottling (Assay)
Acceptance Criteria: 95.0 % - 105.0%.
Table: Results of Assay.
B. No. A1 B. No. A2 B. No. A3
102.5 102.4 102.1
Compressed tablets were packed in heavy weight round HDPE bottle.
Samples were withdrawn from each batch and tested for Assay by using HPLC.
The results of assay for Batch No. A1, A2 and A3 were 102.5, 102.4, 102.1 respectively.
All the results were found within specification limit.
CONCLUSION
The review of data shows compliance to the requirements as per the protocol hence it can
be concluded that this process validation exercise is acceptable.
Hence we concluded that the set procedure which is recommended for manufacturing of
Trandolapril tablets 1mg is followed as such. This process give the product meeting its
pre-determined specifications, quality attributes etc.
The above mentioned recommendations for individual processing step of Trandolapril
tablets 1mg are to be implemented and according to this validation batch records should
be modified.
The updated Batch Manufacturing Records & Batch Packing Records should be used for
the routine manufacturing & packing of the various batches.
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