This document discusses the validation of dissolution test apparatus. It begins with a brief history of validation and reasons for validating equipment. Validation ensures equipment operates consistently and accurately. The document then discusses various types of dissolution test apparatus and the qualification process, including design, installation, operational, and performance qualification. It also addresses sources of error and concludes that acceptable qualification demonstrates the apparatus is validated for use in dissolution testing.

1. Presented By-
Miss S. M. Kumbhar
Under the Guidance of-
Dr. A. S. Kulkarni
1

2. VALIDATION
History-
 Concept of validation was first proposed
by FDA officials in 1970, by Ted Byers &
Bud Loftus.
 Concept was first develop for equipment
and process.
2

3. REASONS FOR VALIDATION
 To improve Quality of
Pharmaceuticals
 To design system properly to
provide high degree of assurance.
3

4. VALIDATION
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.
4

5. Validation
Equipment
Validation
Facilities
Validation
HVAC
Validation
Cleaning
validation
Process
validation
Analytical
Method
Validation
Computer
System
Validation
5

6. DISSOLUTION
 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.
6

7. NEEDS OF DISSOLUTION
TESTING
1. To ensure continuity of product quality &
performance of manufacturing process
2. Requirement for regulatory approval for
product marketing
Dissolution testing is conducted
using dissolution test apparatus
7

8. Validation of dissolution test
apparatus.
Why???
8

9. To have a high degree of assurance
dissolution apparatus should be
consistence and accurate in its
performance.
Therefore validation of this equipment is
required.
.
Validation of Dissolution Test
Apparatus9

10. QUALIFICATION
To ensure that equipment is fit for intended
purpose,
there are no. of qualifying steps that vendor /
analyst
should apply to analytical instruments.
Equipment is evaluated through these tests &
successful
completion justifies instrument operates and
performs
10

11. Fig.No.1 Steps of Qualification11

12. DESIGN
QUALIFICATION
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.
12

13. INSTALLATION
QUALIFICATION
Used to verify that instrument has assembled
in the appropriate environment & its
functioning according to predefined set of limit.
Example-
Setting up fully automated dissolution testing
apparatus requires: proper plumbing, hot water
source, stable bench top.
13

14. OPERATIONAL
QUALIFICATION
During this qualification analyst or vendor
assess that
equipment works as specified & generates
documented data.
Example-
For dissolution water bath temperature, shaft
rpm
speed would be obvious operational parameters
14

15. PERFORMANCE
QUALIFICATION
This is conducted to ensure that system is in
normal
operating environment & performing designed
set of
tasks within the specifications.
Example-
Centering, wobble, height of paddle or basket
attached to shaft, speed, temperature
15

16. DISSOLUTION TEST
APPARATUS
NON -
COMPENDIAL
COMPENDIAL
NON –COMPENDIALEQUIPMENTS:
Rotating bottle, mini paddle, mega paddle, beaker method, peak
vessel, diffusion cells, chewing gum apparatus etc.
COMPENDIAL EQUIPMENTS:
USP Apparatus 1-7
16

17. NON –COMPENDIAL
EQUIPMENTS
17

18. COMPENDIAL
EQUIPMENTS
Apps.
No.
USP IP
1 Rotating basket Paddle assembly
2 Paddle Assembly Rotating basket
3 Reciprocating cylinder
4 Flow through cell
5 Paddle over disk
6 Cylinder
7 Reciprocating holder
18
Table No. 1 Compendial Equipment

19. QUALIFICATION OF NON-COMPENDIAL
EQUIPMENT
If equipment is commercial product IQ and OQ
can be
obtained from the equipment vendor which
includes
vendor specification and tolerances for equipment.
But if equipment is in-house design then process
becomes difficult.
We have to look at adjustments & moving parts,
obtain
operational parameters i. e. agitation rate, flow
rate,
19

20. METHODS
A] Calibration
 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
irregularities.
20

21. B] HYDRODYNAMICS
Dissolution fluid flow should be free from
irregularities
or variable turbulence.
Highly variable data may be unsuitable for that
product.
C] OTHER CONSIDERATIONS-
Ruggedness should be thoroughly evaluated
before
considering transferring product testing to
another site.21

22. APPARATUS SUITABILITY
TEST
• 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
22

23. QUALIFICATION OF COMPENDIAL
EQUIPMENT
A. Calibration or apparatus suitability test:
Calibrator tablets are required
B. Heating jacket
C. Peak vessel
D. Clip & clip less baskets
E. Sinkers
F. Deaeration
G. Automated sampling
H. Single entity with two part detachable shaft
design
23

24. PEAK
VESSEL
 Designed to eliminate
mounding or coning by
having a cone molded
into the bottom of glass
vessel.
 Used when product
contains dense
excipients that have
tendency to cone.
Fig.No.2 Peak vessel
24

25. Clip And Clip Less Basket
 These two types of
basket designs are
commercially available.
 As prednisone
calibrator tablet showed
higher dissolution rate
with three pronged
apparatus it’s the official
design of USP.
Fig.No.3
Basket attachment designs
Left: : o ring
Right : three pronged
25

26. Drawbacks of O Ring And Three Pronged Apparatus
Design
O ring design
 In Robotic dissolution
tester, robotic arm
can remove o ring
type basket more
efficiently
 Gives different
results than 3
pronged apparatus
Three pronged
apparatus design
 Clips disturbs the
fluid flow in the
vessel
 Can weaken
overtime
 Causes basket to
attached too loosely
to shaft & increases
the wobble
26

27. SINKERS
 Used for sticking or
floating of dosage
forms
 Many other sinkers
are available
commercially
 Validated sinkers are
used, any of the
design could be
consider
Hand made sinker
Sinker required in Japanese
pharmacopoeia
27Fig.No.4 Sinkers

28. DEAERATION
 Designed to remove air
bubbles.
 Mechanism: Thin film
vaccum is used,
preheated media is
sprayed using spray-
disbursing nozzle into
closed vessel, vaccum is
applied to remove gases.
Fig.No.5
Deaeration equipment
28

29. Automated Sampling
shaft
prefilter
Fig.No.6 Automated sampling with hollow shaft
29

30. ROTATION SPEED STUDY
 This study should be conducted during OQ
 Study includes measurement of speed of shaft
rotation.
 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.
30

31. TEMPERATURE DISTRIBUTION
STUDY
 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
monograph/1hr.
 Temperature of apparatus 1, 2, 3, 4 = 370 c ± 0.50
c
 Temperature of apparatus 5, 6 = 320 c ± 0.50 c
31

32. SOURCES OF ERRORS
1. Drug substance properties
2. Drug product properties
3. Equipment
4. Method consideration
5. Observation
6. Automation
7. Cleaning
8. Method transfer
32

33. SOURCES OF ERRORS
A] Drug substance properties
e.g. Solubility, pH
B] Drug product properties
Mechanical, formulation
C] Equipment
Mechanical & chemical aspects, Apparatus suitability test
D] Method consideration
To avoid errors
Film coated tablets-sticky-sinker
Suspension-syringe/pipette/beaker
Medium-volume difference
Presence of surfactants
33

34. SOURCES OF ERRORS
E] Observation
Sinkers-turns of wire helix-its effect
Manual sampling
F] Automation
Problems-disconnection, inadequate cleaning, mix-ups
G] Cleaning
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.
34

35. CONCLUSION
At the conclusion acceptable OQ, IQ, PQ, DQ
the dissolution apparatus is considered,
validated and acceptable for use to perform
dissolution testing.
35

36. REFERENCES
• Abdou H. M. (1989). Dissolution, Bioavailability &
bioequivalence (pp.5-33,73-100). Easton Pennsylvania:
Mack publishing company.
• Ansel H. C., Popovich N. G.,& Allen L. V. (2010).
Pharmaceutical Dosage Forms and Drug Delivery Systems
(pp.151-153) Baltimore, Maryland: Lippincott Williams.
• Dressman J., & Kraimer J. (2005). Pharmaceutical
dissolution testing (PP.39-67) Singapore, New York: Taylor &
Francis Group.
• Frost S. M. A. (2004, Feb).Introduction to validation of
Dissolution apparatus (pp.19-21).Dissolution technology.
• Indian Pharmacopoeia (2007). Government of India, Ministry
of Health and Family welfare (vol -I, 179-181), Ghaziabad:
The Indian Pharmacopoeia Commission
36

37. REFERENCES
• Lachman L., Lieberman, & Kanig (2009).Theory and
Practice of Industrial Pharmacy (pp. 301-303,832-833), CBS
Publishers & Distributors.
• Martin A (1991). Physical Pharmacy, physical chemical
principles in pharmaceutical science (pp.352, 408-412),
Mumbai: K. M. Varghese company.
• Nash R. A., Berry I. R. (3rd ed). Pharmaceutical process
validation, Peither T. L., Equipment and facility (vol-129,
pp.443-463). New York: Marcel Dekker.
• The United States Pharmacopeia National Formulary ( USP
24, NF 19). Twinbrook parkway, Rockville: United States
Pharmacopeia Convention (pp.1941-1943)
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