Includes various methods developed in dissolution techniques along with a case study.

1. AA PPrreesseennttaattiioonn OOnn
DDEEVVEELLOOPPMMEENNTT
OOFF DDIISSSSOOLLUUTTIIOONN
MMEETTHHOODD
By Akansha S. Bagde
First Year M. Pharm
Bharati Vidyapeeth’s College of Pharmacy,CBD

2. 2
IINNTTRROODDUUCCTTIIOONN
Dissolution is a technique in which a solid substance
solubilises in a given solvent i.e. Mass transfer from the
solid surface to the liquid phase. It is an analytical
technique employed to measure the release profile from
dosage forms such as tablets and capsules.
Rate of dissolution is the amount of drug substance
that goes in solution per unit time under standardized
conditions of liquid/solid interface, temperature and
solvent composition.

3. THE PROCESSES INVOLVED IN DISSOLUTION OOFF SSOOLLIIDD DDOOSSAAGGEE
FFOORRMMSS:
3

4. A Dissolution test is an in vitro analytical test used for
assessing expected drug release characteristics of
pharmaceutical products in humans, in particular, of
solid oral dosage forms, such as tablets and capsules.
The rationale for conducting these tests is that, for a
product to be therapeutically effective, the drug
(active pharmaceutical ingredient or API) must be
released from the product and should generally be
dissolved in the fluids of the gastrointestinal (GI)
tract.
4

5. The API in solution form facilitates the absorption of
the drug from the GI tract into the systemic (blood)
circulation to reach its desired target (site of action) to
exert its effect.
The basic destination of dissolution testing is to allow the
measurement of bioavailability of a dose in addition to
bioequivalence of batch to batch and bridging to safety
and efficacy aspect. Hence properly organized dissolution
test is necessary for biopharmaceutical formulations.
5

6. FACTORS EFFECTING DDIISSSSOOLLUUTTIIOONN TTEESSTT
 Re lating to Disso lutio n Te st Apparatus:
• Design, size (several ml to serve litres), shape of the
container (round bottom or flat),
• Nature of agitation (stirring, rotating or oscillating
method).
• Speed of agitation.
• Performance precision of the apparatus, etc.
6

7. FACTORS EFFECTING DDIISSSSOOLLUUTTIIOONN TTEESSTT
 Re lating to the Disso lutio n Fluid:
• Composition (water, 0.1N HCL, phosphate buffer,
stimulated gastric fluid, stimulated intestinal fluid).
• Viscosity .
• Volume (larger than that needed to completely dissolve
drug under test).
• Temperature (constant at low temp).
• Maintenance of sink or non-sink conditions.
7

8. FACTORS EFFECTING DDIISSSSOOLLUUTTIIOONN TTEESSTT
Re lating to Pro ce ss Parame te rs:
• Method of introduction of dosage form.
• Sampling techniques.
• Changing the dissolution fluid, etc.
8

9. NNEEEEDD FFOORR DDIISSSSOOLLUUTTOONN
1. Results from in-vitro dissolution rate experiments can
be used to explain the observed differences in in-vivo
availability.
2. Most sensitive and reliable predictors of in-vivo
availability.
3. To ensure quality of product, bioavailability of product
between batches and batch-to-batch quality equivalence
both in-vitro and in-vivo.
4. Serve as quality control procedures, once the form of
drug and its formulation have been finalized
9

10. KEY ELEMENTS OOFF DDIISSSSOOLLUUTTIIOONN
Dissolution is made up of 3
components:
• Inert vessel
• Rotating Shaft
• Dissolution Media
Proper Alignment is key to
ensuring consistency
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11. DISSOLUTION MMEETTHHOODD GGOOAALLSS
A successful dissolution method will be:
• Discriminatory
• Robust
• Correlated to In Vivo
• Transferrable
• Controlled Variability
11

12. DISSOLUTION AAPPPPAARRAATTUUSS SSEELLEECCTTIIOONN
The selection of apparatus is based on formulation design
and practical aspects of dosage form performance in the
in vitro test arrangement.
 Dissolution testing is carried on equipment which has
suitableness such as described in United States
Pharmacopeia (USP) under the charters of Dissolution
and Drug discharge.
12

13. 13
VARIOUS AUTHORIZED TYPES OF DISSOLUTION AAPPPPAARRAATTUUSS
USP Apparatus Apparatus Name Rotation Speed
(rpm)
Dosage Forms
I Basket method 50-100 Solid oral dosage forms
like tablets and capsules
II Paddle method 50-75 Solid oral dosage forms,
oral suspensions and
oral disintegrating
tablets
III Reciprocating
cylinder
6-35 Bead type modified
release dosage forms
IV Flow through cell - Modified release dosage
forms, that contain API
with limited solubility
V Paddle over disc 25-50 Transdermal patches
VI Cylinder - Transdermal
VII Reciprocating holder 30 Non-disintegrating oral
modified-release dosage
form

14. 14
OFFICIAL USP DISSOLUTION AAPPPPAARRAATTUUSS

15. DISSOLUTION MMEETTHHOODD DDEEVVEELLOOPPMMEENNTT
The source of the variability should be investigated.
Attempts should be made to reduce variability whenever
possible.
The two most likely causes are:
• Formulation.
• Artefacts associated with the test procedure.
Visual observations are often helpful for understanding
the source of the variability and whether the dissolution
test itself is contributing to the variability.
15

16. DDEEAAEERRAATTIIOONN ::
Air bubbles can act as a barrier to the dissolution process if
present on the dosage unit or basket mesh and can adversely
affect the reliability of the test results.
Bubbles can cause particles to cling to the apparatus and
vessel walls.
Typical steps include:
• Heating the medium
• Filtering
• Drawing a vacuum for a short period of time.
Media containing surfactants usually are not deaerated
because the process results in excessive foaming.
16

17. DDEEAAEERRAATTIIOONN ::
Common Deareation Methods:
• USP Vacuum Filtration Method (default unless
another approach is validated)
• Helium Sparging*
• Automated Degassing*
• Superheating*
• Not Degassing At All*
Unacceptable Methods:
• Nitrogen Sparging
• Sonication
*when validated against USP method
17

18. SSIINNKKEERRSS::
Sinkers are often used to adjust the buoyancy of dosage
forms that would otherwise float during testing with
Apparatus 2.
Sinkers are typically used to keep the dosage form at the
bottom of the vessel but they can also be used to keep
dosage forms from sticking to the vessel (e.g., film-coated
tablets).
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19. SSIINNKKEERRSS::
 General guidelines to consider when choosing a sinker for your
application include:
• Sinker Size - the sinker should have minimal surface contact with
the tablet as this can affect the dissolution rate.
• Sinker Weight - should be kept to a minimum - just enough to
have a desired effect.
• PTFE Coated Sinkers Magnetic - used with magnetic retrieval
systems, or where there may be a reaction between steel and the
tablet.
• Uncoated - type 316 stainless steel sinkers are more durable than
coated sinkers.
• Basket Sinkers - can be used but care should be taken that the outer
coating of the tablet does not clog the mesh
• Wire Spirals - should be as wide as practically possible to avoid
clogging. 19

20. AAGGIITTAATTIIOONN ::
For immediate-release capsule or tablet formulations
should be sufficient to allow for media to interact with
dosage form.
Too much agitation can result in non-discriminatory
profiles.
• Apparatus 1 (baskets) at 50–100 rpm
• Apparatus 2 (paddles) at 50 or 75 rpm are used most
commonly
Agitation rates between 25 and 50 rpm are generally
acceptable for suspensions.
Coning (mounding) can be reduced by increasing the
paddle speed to 75 rpm.
20

21. SSAAMMPPLLIINNGG::
Autosampling is a useful alternative to manual sampling,
especially if the test includes several time points.
Sampling probes or fiber- optic probes can disturb the
hydrodynamics of the vessel.
Sampling probes should pull the sample from the
sampling zone.
The position of the pharmacopeial sampling zone for
Apparatus 1 and Apparatus 2 is midway from the top of
the stirring element to the medium surface and depends
on the medium volume.
The programmed sampling volume depends on the dead
volume of the tubing, cuvettes, and other devices and has
to be adjusted accordingly.
21

22. SSAAMMPPLLIINNGG::
How To Sample Properly
Filtration Must Occur at USP
Location and at Appropriate Time
•+/-2% from timepoint or 15 minutes
(whichever less).
•Halfway between top of paddle or
basket and media.
•No closer than 1cm to vessel wall.
•Recommend not sampling close to
shaft due to poor hydrodynamics.
22

23. FFIILLTTEERRSS::
Filters are used to trap particles of tablet from the sample
and prevent them getting into the spectrophotometer.
Different types of filters used are:
• Cannula filters - used when high levels of particulate are
present
• Filter Discs - Low volume sample probes may require an
In-Line Filter Disc. These are designed to keep the
filtration process outside the vessel.
• Filter Tips - smaller than cannula filters, filter tips fit on
the end of larger diameter sample probes.
Centrifugation is not a replacement for filtration.
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24. FFIILLTTEERRSS::
HOW DO I VALIDATE A FILTER?
3 Factors Should Be Tested:
• Efficiency– does it remove undissolved drug?
• Leachability – does it leach a coeluting peak?
• Adsorbance – does the filter hold drug?
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25. FFIILLTTEERRSS::
 Efficiency:
• Take 3 samples with filter
• Sample 1 – scan immediately
• Sample 2 – sonicate 5 minutes and read
• Sample 3 – sonicate 10 minutes and read If <1% increase, filter is
acceptable
 Leachability:
• Take filtered sample of blank media If there is a peak >1% of
standard response then a different filter is needed or a pre-rinse
 Adsorbance :
• Filter standard in small aliquots, 1mL at a time and analyze
individually. When you reach 99% recovery, filter has been
properly filtered. Method will need to define amount to waste.
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26. CCLLEEAANNIINNGG ::
After change of dissolution medium and/or product
during the sequence of tests, it may be advisable to
reconsider cleaning.
The condition of the vessels can affect the results, and
effective cleaning will return them to a suitable state.
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27. CCLLEEAANNIINNGG ::
Cleaning is often not validated to ensure that it is
effective in:
• Removing drug from dissolution unit from previous
run
• Removing residues from surfaces and sampling paths
• Preventing corrosion
27

28. CCLLEEAANNIINNGG ::
Cleaning the Apparatus
• Clean as soon as possible after run.
• Soap and Water usually effective.
• Raise head and clean spindles .
• Remove vessels, back first .
• No abrasives.
• Handle baskets with care. (sonicating in alcohol
preferred)
• Replace components to bath or proper storage containers.
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29. RREELLAATTEEDD AARRTTIICCLLEE::
Research Journal Of Pharmaceutical, Biological And Chemical Sciences
Development Of Dissolution Medium For Poorly Water Soluble Drug Mefenamic
Acid
Pradnya B. Patil, V. R. M. Gupta, R. H. Udupi, K. Srikanth, B. Sree Giri Prasad
 Mefenamic acid’s oral bioavailability is very low, probably due to
poor solubility in water and insufficient dissolution rate. As a result
a dissolution medium was developed.
 Approaches usually used in the design of dissolution media for
poorly water soluble drugs include:
a) Bringing about drug solubility by increasing the volume of the
aqueous sink or removing the dissolved drug.
b) Solubilization of the drug by co-solvents, up to 40% and by anionic
or non-ionic surfactants by adding to the dissolution medium in
post micellar concentrations.
c) Alteration of pH to enhance the solubility of insoluble drug
molecules. 29

30. • The objective of the present study is to develop suitable
dissolution medium, which satisfies sink condition, for
testing Mefenamic acid formulations by adding co-solvents
or surfactants.
• Since Mefenamic acid is water insoluble hence the
solubility studies were carried out in different mediums. The
data revealed that the solubility of Mefenamic acid is least
in water and its solubility is maximum in water containing 2
% w/v of SLS.
As on increasing the pH of water, the solubility of
Mefenamic acid is increased. The solubility is further
increased on addition of co-solvent and surfactants.
Surfactants enhance the solubility of Mefenamic acid in
water than the co-solvent (methanol).
30

31. SLS has shown better results than the tween- 80.
Hence, the solubility of Mefenamic acid in water
containing various concentrations of SLS has been
studied by withdrawing samples at intervals and analyzed
spectrophotometrically at 285nm.
Among all the solubility of Mefenamic acid is more in
water containing 2% w/v SLS.
The improved dissolution profile of Mefenamic acid in
surfactant containing SLS may be due to the fact the
surfactants enhances the dissolution of pure drug by
facilitating the drug release process at the solid/ liquid
interface and micelle solubilisation in the bulk.
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