Presentation about dissolution apparatus testing machine for tablet and new version which is manufactured by lab 8 "Industrial Pharmacy Course" faculty of pharmacy october 6 university. we added new modification which is already applied and others not applied due to high cost but suggested. and all modifications are approved from industrial pharmacy department O6U.

1. Dissolution Apparatus
Yasser Mohamed Sedik
5th Level
2018

2. Topics Outline
1- Introduction
2- Dissolution Apparatus
3- Our Machine "PBSI Version“
4- Cleaning
5- Components & Validation Material
6- References

3. Introduction
1- What is the Dissolution Apparatus ??
2- Difference Between Drug Release &
Dissolution
3- Purposes of Dissolution Apparatus
Test
4- In-Vitro In-Vivo Correlations “IVIVC”

4. What is the Dissolution Apparatus ??
▪ Tablet Dissolution is a standardized method for measuring the rate of
drug release from a dosage form
▪ In the pharmaceutical industry, drug dissolution testing is routinely
used to provide critical in vitro drug release information for both
quality control purposes, i.e., to assess batch-to-batch consistency of
solid oral dosage forms such as tablets, and drug development, i.e., to
predict in vivo drug release profiles.

5. Difference Between Drug Release & Dissolution
▪ Dissolution test is normally used to describe the testing of those forms
such as immediate release oral tablets or capsules intended to dissolve
rapidly in the test medium.
▪ For non-oral dosage forms such as semisolids, suppositories, topical
and transdermal systems, the term “drug release” is normally
employed.

6. Purposes of Dissolution Apparatus Test
1. Quality-control and quality-assurance purposes
2. In early phase drug development
3. Assess product stability, monitor formulation changes over time
4. Establish in-vitro–in-vivo correlations "IVIVC"
5. Regulatory perspective
Particularly in the development and approval of generic dosage forms

7. In-Vitro In-Vivo Correlations “IVIVC”
▪ defined by the U.S. Food and Drug Administration (FDA) as "a
predictive mathematical model describing the relationship between an
in-vitro property of a dosage form and an in-vivo response".
▪ The United States Pharmacopoeia (USP) also defines IVIVC as "the
establishment of a relationship between a biological property, or a
parameter derived from a biological property produced from a dosage
form, and a physicochemical property of the same dosage form".
▪ Parameters of Biological Property “AUC, Cmax”
Physicochemical Property is the “Dissolution Profile”
▪ The main role of IVIVC
1- To use dissolution test as a surrogate for human studies.
2- To supports and/or validate the use of dissolution methods and
specifications.
3- To assist in quality control during manufacturing and selecting
appropriate formulations

8. Dissolution
Apparatus
1- Factors affecting dissolution
2- The Performances of Dissolution
Apparatuses
3- Different types of dissolution apparatus
according to the pharmacopeias
4- Dissolution Apparatus-1 “Basket
Apparatus”
5- Dissolution Apparatus-2 "Paddle Type“
6- Dissolution Apparatus-3 "Reciprocating
Cylinder“
7- Dissolution Apparatus-4 "Flow through
Cell“
8- Dissolution Apparatus-5 "Paddle over
Disc“
9- Dissolution Apparatus-6 "Rotating

9. Factors Affecting Dissolution
1. Intrinsic properties of the API (e.g., solubility, wettability, particle
size, surface area, morphology, polymorphs).
2. The formulation composition and characteristics (e.g., excipients,
hardness, manufacturing process)
3. The dissolution method used for its assessment (e.g., apparatus,
medium, test conditions, sampling, and sample analysis).

10. The Performances of Dissolution Apparatuses
1. Hydrodynamics its physical property interested mainly with the
mechanics of fluid and pressure applied on the particles inside the
fluid.
2. The designs of the dissolution apparatuses
3. The ways of operating dissolution apparatuses
have huge impacts on the hydrodynamics
Note: Hydrodynamic studies in dissolution apparatuses were carried out
by researchers over the past few years with both experimental methods
and numerical modeling such as Computational Fluid Dynamics (CFD).

11. ▪ Dosage form to be effective must have ability to pass into the systemic
circulations then to the site of activity, and this process have 2 main
definitions “Dissolution, Absorption”.
▪ Dissolution: is the process of extracting the API out of the dosage
form.
Absorption: is the process of transporting the drug substance from the
gastrointestinal lumen into the systemic circulation.
▪ Dissolution testing method is the characterized method that provide in
vivo dissolution information but doesn’t provide information about
drug substance absorption.
▪ A dissolution method should have adequate discriminatory power to
detect formulation changes that affect the dissolution rate of a drug
product.

12. Different types of dissolution apparatus according to the
pharmacopeias
I.P U.S. P B. P E. P
Type 1 Paddle
Apparatus
Basket
Apparatus
Basket
apparatus
Paddle
apparatus
Type 2 Basket
Apparatus
Paddle
Apparatus
Paddle
apparatus
Basket
apparatus
Type 3 Reciprocating
Apparatus
Flow through
cell apparatus
Flow
through cell
apparatus
Type 4 Flow through
cell Apparatus
Type 5 Paddle over
disk apparatus
Type 6 Rotating
Cylinder
Type 7 Reciprocating
holder

13. Dissolution Apparatus-1 “Basket Apparatus”
▪ Adopted in 1970 the rotating basket method of dissolution testing
was the first official method.
▪ Design:
Vessel: Made of Borosilicate Glass Semi Hemispherical Bottom,
Capacity 1000 ml.
Shaft: Stainless Steel 316, Speed 50 – 100 RPM.
Water Bath: Maintained at 37 +/- 0.5*C
Dosage Form is kept in the basket.
▪ Used For:
- Beads (use a finer mesh basket where appropriate)
- Capsules (preferred over Apparatus 2)
- Orally disintegrating (Orodispersibles)
- Tablets

14. Dissolution Apparatus-2 "Paddle Type"
▪ The dosage form is dropped directly into the medium, which is stirred
by means of a paddle attached to the stirring shaft, rotated typically at
50 or 75 rpm
▪ Design:
Shaft: Fused with blade bottom
Stirring element: Coated with Teflon for laboratory purposes,
Stainless Steel is used.
Rotation speed: 25-50 RPM
Water Bath: Maintain at 37 +/- 0.5*C
Sinkers: Platinum wire use to prevent tablet/capsule from
floating.
▪ Used For:
- Capsules
- Powders
- Suspensions
- Tablets (preferred over Apparatus 1)

15. Dissolution Apparatus-3 "Reciprocating Cylinder"
▪ Is a very versatile device for the in vitro assessment of release
characteristics of solid oral dosage forms, because it enables the
product to be subjected to different dissolution media and agitation
speeds in a single run.
▪ Used for:
- Tablet
- Beads
- Controlled& Extended release formulations

16. Dissolution Apparatus-4 "Flow through Cell"
▪ In the closed system configuration, the flow-through cell enables the
performance of a dissolution test with a low amount of media in order
to achieve the necessary testing environment.
▪ Used for:
- Low Solubility drug.
- Micro particulate
- Implants Suppositories
- Controlled release formulations.

17. Dissolution Apparatus-5 "Paddle over Disc"
▪ A variation on Apparatus 2. The dosage form is applied to a stainless-
steel disk or watch glass, which is then placed in, the bottom of the
vessel prior to being stirred in the conventional manner. Test at 32
degrees C and pH 5-6 to reflect skin conditions.
▪ Used For:
- Transdermal Patches "Drug Release Studies"
- Products involving delivery through the skin.

18. Dissolution Apparatus-6 "Rotating Cylinder"
▪ The rotating cylinder which has specific advantages over the paddle
over disk methods and reciprocating holder apparatus. The rotating
cylinder apparatus is designed to handle much larger patches, while
holding the patch to the cylinder wall during the test. This talk will
explore the advantages as well as cover the practical use of the
apparatus.
▪ Used For:
- Mainly Transdermal Product

19. Dissolution Apparatus-7 "Reciprocating Holder"
▪ This unit is perfectly suited for simulating the pH-changes within the
human body. By placing different media in each row, the device
echoes varying in vivo gastrointestinal conditions of the body.
▪ An automatic sample transport between the rows allows the reliable
testing of the extended or sustained release from different dosage
forms in various pH-zones. The simple to program RRT 10 thus, is the
perfect unit for multiple media pH-changes for IVIVC testing and
dissolution profiling of a variety of release dosage forms "e. g. tablets,
coated tablets and oblongs".
▪ Used For
- Controlled release dosage form
- Non-disintegrating oral formulations

20. Dissolution Apparatus -
PBSI
1- What is the PBSI Mean ?
2- Advantages & Disadvantages
3- Material
4- Applied Modifications in our Machine
5- Suggested Modifications
6- Standard Operating Procedure "SOP"

21. What is the PBSI Mean ?
▪ Our machine is different as it works 4 in 1 by using four additions
▪ Paddle
They made from Stainless Steel 316
Rotated typically at 50 or 75 rpm
Used for: Capsules, Powders Suspensions and Tablets
▪ Basket
they made from Stainless Steel 316
Rotated typically at either 50 or 100 rpm
Used for: Beads, Capsules, Tablets

22. ▪ Basket Suppositories
Normal basket but used mainly for suppositories.
▪ In-Vivo absorption detection
we will use a piece of rabbit intestines to measure the absorption as
the intestine like our skin.
Absorption of substances through the skin depends on a number of
factors the most important of which are :
concentration, duration of contact solubility of medication, and
physical condition of the skin.
Then we will be able to quantify the absorbed drug.

23. Advantages & Disadvantages
▪ Advantages:
1- Better reproducibility.
2- Easy to clean.
3- PH change possible.
4- Can be easily automated which is important for routine
investigation.
5- Easy in detection absorption of the drug
6- Easy and accurate in sampling method
▪ Disadvantages
1- Tendency of light particles to float at surface
after leaving baskets or in paddle method.
2- Sensitivity of apparatus to variables such as vibrations, eccentricity.
3- Rapid corrosion of SS mesh in presence of HCl.
4- Sensitivity of apparatus to any slight changes in paddle orientation.

24. Material
▪ Body of the motor – Sheet of metal
▪ Shafts – Stainless steel 316
▪ Paddle & Basket - Stainless steel 316.
▪ Water Bath – Securit glass
▪ Vessel - Borosilicate glass

25. Applied Modifications in our Machine
▪ In Vivo Basket "Absorption & Penetration Detection“
This idea depending on analyze the amount of dissolute particles
absorbed by intestine or skin, the dissolute particles will pass from
part of media to all media available through skin or intestine, and we
compared it with results from regular basket apparatus.
Another modification in this topic we will suspended the part from
intestine or skin in the media and will assay the amount of drug
absorbed by determination the amount of drug particles in the media
by normal apparatus then compared with the concentration of the dug
in this media.

26. ▪ Sampling
We added Syringe for each vessel which are stable and connected to
vessel by specific needle which are immovable and constant and end
of it in the media.
▪ Brush for Cleaning
a very soft brush added on the end of the shaft at the place of paddle
or basket which main objective to clean the vessel

27. Suggested Modifications
▪ Moving Shaft by Pressure
Making new shaft tool which moving by pressure from the upper side
useful in save money alternatively the automatic machine and have a
good appearance.
▪ HPLC Connection
The connection part from the media in vessel and HPLC by using
different auto samplers.
This led to decrease time in handling the sample and inject it in
the HPLC and can identify the concentration of the drug in
the media rapidly.

28. ▪ In Vitro Dissolution Absorption System (IDAS)
IDAS provides the ability to evaluate absorption, permeation,
accumulation, biomarker regulation and metabolism, as well as the
ability to test a finished dosage form from a tablet, capsule to
suspension.
▪ Consists Mainly From
1- Two L-Shaped Chamber
2- Buffer mimicking the protein ion and glucose content in the Plasma
of human blood 3- Caco-2 Layer which fixed in the end of the
chamber they are intestinal Human cells used mainly in research of
absorption system.
4- Special vessel "500 ML"
▪ Samples are taken normally from the open in the cover of
the vessel to assay the dissolution in the same time
we take sample from the eye of the chamber
to detect the absorption

29. ▪ Protection the Paddle or Basket
We can cover the paddle or basket by using the Gold, Titanium, and
PTFE.
are very important in preventing corrosion
▪ Vibrator in Water Bath
The vibrator make a very low moving in the water which keep it in the
movable phase and prevent the salts and other adulterants from
precipitation on the wall.

30. Standard Operating Procedure "SOP"
1. Switch „ON” the power, instrument will initialize.
2. Press the RPM, TEMP, TIME, and OPTN keys from the front panel to
set the parameters of the test.
3. Change protocol no. using Increment / Decrement keys.
4. Press the ENTER key to register the set parameter in the protocol,
such 20 protocols can be prepared.
RPM Settings
1. Press the RPM key from the front panel. Set the RPM from 25 to 200
using the UP / DOWN / DIGIT SCROLL key as per requirement.
2. To start or stop the stirrer use F1 or F2 keys respectively.

31. Temperature Setting:
1. Press the TEMP key from the front panel. Set the temperature from
30.0°C to 40.0°C by using UP / DOWN / DIGIT SCROLL key.
2. Switch heater ON/OFF BY using the function key F1/F2 Press ENTER
key to register the change.
3. “TEMP ON” LED on the front panel will glow after switching on heater.
The pump and the Heater ON LED on temperature Controller Unit will
glow.
Dissolution Medium Preparation:
Prepare the dissolution medium as per specified under monograph or
procedure, filter through 0.45 mm filter paper under vacuum and
stirring.
Note: Replace the water from the bath weekly or early if required
Sample Withdraw Procedure:
Withdraw sample from a zone midway between the surface of the
dissolution medium and top of rotating basket/paddle, not less than 10

32. Cleaning
1- Paddles and Basket Shafts
2- Baskets
3- Vessels
4- Cannulas
5- Auto samplers
6- Important Notes

33. Paddles and Basket Shafts
▪ Clean with soap and water. A paper towel with soapy water can be
used to clean the shafts, and then followed with a squirt bottle of DI
Water.
▪ If the product or media is viscous in any way, you may need to use
alcohol or other products as well.
▪ If polymer is left on the shafts, it will also have acid/salt/etc. of the
media with it which will concentrate and lead to rapid rusting.

34. Baskets
1. Rinse them gently in the sink
2. Put them in a beaker with ethanol or methanol and sonicate them for
about 5 minutes.
3. Remove them and allow them to air dry.
4. Place them into a protective container when done.
Baskets should appear shiny, if they appear dull/flat in color (like the
basket pictured on the right of the header picture) it is time to replace
them.

35. Vessels
▪ Clean with soap and water, and a non-abrasive washcloth or other
item.
▪ When removing from the dissolution bath, remove back vessels first to
reduce the chance of accidentally spilling your media into your water
bath.
▪ Dishwashers are acceptable for glass-lipped vessels, but may not be
for plastic-lipped ones.

36. ▪ Cannulas - Treat these the same as shafts. Cannulas are often
overlooked when cleaning.
▪ Auto samplers -
- DI Water works best for salts, sugars, and surfactants. you can heat
DI Water to 50-60C to improve solubilization of residues in lines.
- Alcohols work well for polymers and difficult to clean products.
- Some auto samplers, such as the Agilent 850-DS, can have an
integrated auto clean which will occur immediately after the final time
point to prevent drying.

37. Important Notes
1. Clean as soon as possible after a run is complete
- prevents drying or precipitation of your drug, excipients, and
media components in tubing
- it reduces the attack of acids on stainless steel and other
components.
2. don't use any abrasives or anything that could damage the
components
3. The cleaning being performed should be based on the samples
you've run. Different samples and media will often require different
cleaning approaches.
- Surfactants and salts is often cleaned best with DI Water.
- Polymers may require use of alcohols to help clean the system.
- Surfactants/salts/polymers may require several rinses of
Water/Alcohol/Water.

38. Component &
Validation
Material
1- Dissolution Vessel
2- Dissolution Basket
3- Dissolution Paddle
4- Controlling Temperature
5- Capsule Sinkers
6- Controlling Wobble
7- Level and Verticality Issues
8- Centering of Stirring Element
9- Height of Basket or Paddle above Bottom
of Vessel
10- Rotational Speed
11- Dissolution Filters
12- Dissolution Sampling
13- Commonly Used Dissolution Media

39. Dissolution Vessel
▪ Specification
USP For a 1 liter Vessel
Height: 160-210mm.
Outside Diameter: 98-106mm
Hemispherical Bottom
Critical Part of the
Apparatus
Amber vessels are used to reduce the
amount of light that can get into the vessel
for light sensitive applications

40. ▪ Unfortunately all the major bath manufacturers specify different
diameter glass, meaning there is no “one size fits all” vessel.
▪ Vessels should be guaranteed to meet the specification of the original
vessels.
▪ All vessels should be serialized and where possible used in the same
bath location and orientation to minimize the physical differences.
▪ Plastic vessels are easily scratched, crack very quickly and have much
poorer heat transmission than glass vessels
Plastic vessels (or PTFE coated glass vessels) are sometimes used
where the dosage form will stick to a glass vessel.
▪ Because of the poor thermal qualities, to ensure the temperature
inside the vessel remains at 37C the temperature of the water
bath has to be set higher than normal.

41. Dissolution Baskets
▪ Dissolution baskets are a precise and fragile piece of precision
instrumentation and are easily damaged
▪ A good basket should be rigid with no movement.

42. ▪ Simple Test - hold a basket rims between the thumb and forefinger on
both hands and gently twist back and forth. If there is any movement
in the mesh of the basket then there is a real potential that the basket
will easily deform, and worse, that it will not pass the basket wobble
test.
▪ Good baskets are reproducible baskets and reproducibility is the goal
of any dissolution testing.
▪ Baskets should be individually serialized and certified.
▪ Correct handling of baskets is important and avoids both physical
damage and contamination.
▪ The use of a simple basket storage rack, which is both inexpensive
and easy to use, is the best way to ensure that baskets maintain their
integrity during storage.

43. Dissolution Paddle
▪ Most widely used method in dissolution testing, Originally developed
by Poole (1969) and was refined by scientists at the FDA for Drug
Analysis in St Louis.
▪ The dimensions of the paddle are closely controlled. Any variations
can easily have a detrimental effect on reproducibility from vessel to
vessel. For this reason, paddles should be treated as a precision piece
of equipment, stored correctly, and inspected regularly for scratches,
dents or other imperfections.
▪ Coating by PTFE, The purpose of the coating is to reduce the
interaction between steel and the dosage form. As steel quality
improves, the need for coating reduces, but care should be exercised
to use paddles of suitable steel quality.

44. Capsule Sinkers
▪ Floating dosage forms can present a real problem and may be
weighted with a sinker which should be heavy enough to cause it to
sink to the bottom of the vessel.
▪ A sinker is commonly formed from a wire helix.
▪ The USP states “A small, loose piece of non-reactive material, such as
not more than a few turns of wire helix, may be attached to dosage
units that would otherwise float. An alternative sinker device is shown
in Figure 2a. Other validated sinker devices may be used.”
Japanese Sinker
(Figure 2a Ref USP
Above)
Spiral or Coil
Sinker
3 Prong
Sinker
'Sotax Style' Spiral
Sinker
Basket Sinker Breath Film Sinker

45. Controlling Temperature
▪ Specifications:
USP Toolkit: ± 0.5oC but all vessels should agree within 0.4oC
▪ Temperature is critical because it has a linear effect of dissolution
results.
▪ Using a calibrated thermometer, the temperature should be tested in
each vessel prior to each test.
▪ If plastic vessels have to be used, their heat transfer is poor compared
with glass and the water bath temperature will need to be
correspondingly higher.
▪ Factors affect the temperature around the dissolution tester.
1- Heat loss from one end of the bath to the other
2- Inadequate water pumping
3- Air conditioning

46. Controlling Wobble
▪ Specifications:
Shaft Wobble
USP Toolkit: ≤1.0 mm run out, 1 cm above the paddle or basket
Basket Wobble
USP Toolkit: ≤1.0 mm run out at bottom of basket
▪ Wobble is the movement from the center line of a shaft or basket as it
rotates. This causes a disruption in the flow profile in the vessel and
can have a significant impact on dissolution rate.
▪ Measurements are performed using a Wobble meter

47. Level and Verticality Issues
▪ Specifications
Horizontal Level
USP: <0.5° from horizontal at 2 points 90° apart
Shaft Verticality
USP: <0.5° from vertical at 2 points 90° apart
Vessel Verticality
USP: <0.5° from vertical at 2 points 90° apart
▪ Using Digital Protractor to detect the level and verticality

48. Centering of Stirring Element
▪ Specifications
USP Toolkit: ≤2.0 mm, not more than 2 cm below the flange of the
vessel
▪ Centering measures whether the paddle or basket is exactly in the
center of the vessel. If they are not then irregular media flow patterns
can result.
▪ The centering test relies on the fact that the vessels are good, and so
only fully dimensionally certified vessels should be used.

49. Height of Basket or Paddle above Bottom of Vessel
▪ Specifications:
USP: 25mm ± 2mm
▪ Height setting for baskets and paddles is necessary prior to each test.
Although it is part of the qualification process every six months, it
should not be assumed that the height does not change between those
times, and a check before each test ensures that the tester has been
correctly set-up by the operator.
DEPSET-MI
25mm Ball Spacer
DEPSET-25
25mm Spacer
DDAPT-Q
Digital Depth Gauge

50. Rotational Speed
▪ Specifications
USP Toolkit: +/- 1rpm at 50rpm and 100rpm
▪ With current motor technology there is no reason why dissolution
testers should not be within 0.1rpm and certainly 1rpm is easily
achievable.
▪ The simplest way to measure rotational speed is with an optical
tachometer. This reads a reflective marker placed on the spindle. It is
ideal to measure this at both 50 rpm and 100rpm which are the two
most common test speeds.

51. Dissolution Filters
▪ The majority of filters are manufactured from porous Polyethylene or
porous PVDF and are designed to fit on the end of a sampling cannula.
That requires that the hole in the filter is exactly correct for the
diameter of sampling cannula used.
1/8" Standard
Filter
1/16" Standard
Filter
VanKel Style
Filter
Filter with
Color
Coding
Distek Style
Disc Filter
Filter Tip

52. Dissolution Sampling
▪ Sampling can present the opportunity for a number of errors,
especially for multiple point dissolution tests.
▪ Placing sampling devices in the media can have an immediate effect on
the hydrodynamics in the vessel, especially if they are large, such as a
pipette for example.
▪ Sampling Position
The USP states: “Within the time interval specified, or at each of the
times stated, withdraw a specimen from a zone midway between the
surface of the Dissolution Medium and the top of the rotating basket
or blade, not less than 1cm from the vessel wall”
The zone is clearly interpreted as a horizontal area in the vessel.
1cm away from the vessel wall to ensure that the
media is free flowing.

53. Commonly Used Dissolution Media:
▪ Purified water
▪ Dilute acid " 0.001N - 0.1N HCL "
▪ Stimulated Gastric Fluid
▪ Stimulated intestinal fluid
▪ Surfactants " e.g. Polysorbate, SLS "
▪ Aqueous buffers " PH 5-7 "

54. References
▪ http://www.labhut.com/education-centre/about-dissolution-testing.html
▪ http://www.pharmtech.com/dissolution-testing-3
▪ https://slideplayer.com/slide/1595894/
▪ https://www.slideshare.net/pharmaguideline/dissolution-testing-in-pharmaceuticals?qid=2149e606-b0c1-458e-a496-22038a4c378f&v=&b=&from_search=6
▪ https://www.slideshare.net/karankar71/dissolution-testing-apparatus-76645957?qid=2149e606-b0c1-458e-a496-22038a4c378f&v=&b=&from_search=5
▪ https://www.slideshare.net/BShamim/dissolution-testing-apparatus-60496485?qid=2149e606-b0c1-458e-a496-22038a4c378f&v=&b=&from_search=4
▪ http://www.copleyscientific.com/
▪ http://www.erweka.com/
▪ https://www.agilent.com/en/products/dissolution/apparatus/708-ds-dissolution-apparatus
▪ https://www.pharmaguideline.com/2017/11/different-types-of-dissolution-apparatus.html
▪ https://www.usp.org/sites/default/files/usp/document/harmonization/gen-method/stage_6_monograph_25_feb_2011.pdf

55. Thank You
Yasser Mohamed Sedik