Miss S. M. Kumbhar
Under the Guidance of-
Dr. A. S. Kulkarni
Concept of validation was first proposed
by FDA officials in 1970, by Ted Byers &
Concept was first develop for equipment
REASONS FOR VALIDATION
To improve Quality of
To design system properly to
provide high degree of assurance.
Validation is process of establishing
documented evidence that provides high
degree of assurance that specific process will
consistently produce a product meeting its
predetermined specifications and quality.
Process by which known amount of drug
substance goes into solution per unit time
under standardized conditions.
Primary goal- to provide measurements for
bioavailability & to demonstrate
bioequivalence from batch to batch.
NEEDS OF DISSOLUTION
1. To ensure continuity of product quality &
performance of manufacturing process
2. Requirement for regulatory approval for
Dissolution testing is conducted
using dissolution test apparatus
Validation of dissolution test
To have a high degree of assurance
dissolution apparatus should be
consistence and accurate in its
Therefore validation of this equipment is
Validation of Dissolution Test
To ensure that equipment is fit for intended
there are no. of qualifying steps that vendor /
should apply to analytical instruments.
Equipment is evaluated through these tests &
completion justifies instrument operates and
When developing dissolution method DQ is built
into apparatus selection of process,
Dosage form & delivery system will determine
choice of equipment.
Example-first choice for beaded product may be
USP app 3…… as it is designed to confine
beads in a screened-in cylinder.
Used to verify that instrument has assembled
in the appropriate environment & its
functioning according to predefined set of limit.
Setting up fully automated dissolution testing
apparatus requires: proper plumbing, hot water
source, stable bench top.
During this qualification analyst or vendor
equipment works as specified & generates
For dissolution water bath temperature, shaft
speed would be obvious operational parameters
This is conducted to ensure that system is in
operating environment & performing designed
tasks within the specifications.
Centering, wobble, height of paddle or basket
attached to shaft, speed, temperature
Rotating bottle, mini paddle, mega paddle, beaker method, peak
vessel, diffusion cells, chewing gum apparatus etc.
USP Apparatus 1-7
1 Rotating basket Paddle assembly
2 Paddle Assembly Rotating basket
3 Reciprocating cylinder
4 Flow through cell
5 Paddle over disk
7 Reciprocating holder
Table No. 1 Compendial Equipment
QUALIFICATION OF NON-COMPENDIAL
If equipment is commercial product IQ and OQ
obtained from the equipment vendor which
vendor specification and tolerances for equipment.
But if equipment is in-house design then process
We have to look at adjustments & moving parts,
operational parameters i. e. agitation rate, flow
Non-compendial & some compendial apparatus
do not have calibrator tablets, in some case in
house calibrator tablets are designed.
Some unique aspects of equipment can only be
detected with USP calibrated tablets, there are
no practical measuring tools available for
analyst. e.g. vibration and vessel
Dissolution fluid flow should be free from
or variable turbulence.
Highly variable data may be unsuitable for that
C] OTHER CONSIDERATIONS-
Ruggedness should be thoroughly evaluated
considering transferring product testing to
• Used calibrator tablets
• Duration of apparatus suitability test
a) NLT twice a year per equipment
b) After any equipment change
c) After significant repair
d) After movement of assembly
QUALIFICATION OF COMPENDIAL
A. Calibration or apparatus suitability test:
Calibrator tablets are required
B. Heating jacket
C. Peak vessel
D. Clip & clip less baskets
G. Automated sampling
H. Single entity with two part detachable shaft
Designed to eliminate
mounding or coning by
having a cone molded
into the bottom of glass
Used when product
excipients that have
tendency to cone.
Fig.No.2 Peak vessel
Clip And Clip Less Basket
These two types of
basket designs are
calibrator tablet showed
higher dissolution rate
with three pronged
apparatus it’s the official
design of USP.
Basket attachment designs
Left: : o ring
Right : three pronged
Drawbacks of O Ring And Three Pronged Apparatus
O ring design
In Robotic dissolution
tester, robotic arm
can remove o ring
type basket more
results than 3
Clips disturbs the
fluid flow in the
Causes basket to
attached too loosely
to shaft & increases
Used for sticking or
floating of dosage
Many other sinkers
Validated sinkers are
used, any of the
design could be
Hand made sinker
Sinker required in Japanese
Designed to remove air
Mechanism: Thin film
vaccum is used,
preheated media is
sprayed using spray-
disbursing nozzle into
closed vessel, vaccum is
applied to remove gases.
ROTATION SPEED STUDY
This study should be conducted during OQ
Study includes measurement of speed of shaft
Speed should be measured with photo
tachometer for 30 mins.
Speed of shaft rotation should be verified to be
within 4% of speed specified in monograph.
Study should be conducted during OQ
Includes temperature mapping of each vessel
Temp. should be mapped by using data
acquisition system for minimum time as per
Temperature of apparatus 1, 2, 3, 4 = 370 c ± 0.50
Temperature of apparatus 5, 6 = 320 c ± 0.50 c
SOURCES OF ERRORS
1. Drug substance properties
2. Drug product properties
4. Method consideration
8. Method transfer
SOURCES OF ERRORS
A] Drug substance properties
e.g. Solubility, pH
B] Drug product properties
Mechanical & chemical aspects, Apparatus suitability test
D] Method consideration
To avoid errors
Film coated tablets-sticky-sinker
Presence of surfactants
SOURCES OF ERRORS
Sinkers-turns of wire helix-its effect
Problems-disconnection, inadequate cleaning, mix-ups
Many products, same equipment major source of error
H] Method transfer
Sinkers, dispensing apparatus, sampling methods, precise
medium, standard preparations, grade of reagents
should be uniform.
At the conclusion acceptable OQ, IQ, PQ, DQ
the dissolution apparatus is considered,
validated and acceptable for use to perform
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Mack publishing company.
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The Indian Pharmacopoeia Commission
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• The United States Pharmacopeia National Formulary ( USP
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