The workplace ecosystem of the future 24.4.2024 Fabritius_share ii.pdf
A seminar on dissolution media
1. Presented By
Mahajan Pratik Shivram
(M. PHARM. Ist SEM.)
2014-15
DEPARTMENT OF PHARMACEUTICS
R. C. PATEL INSTITUTE OF PHARMACETICAL
EDUCATION & RESEARCH SHIRPUR
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2. INRODUCTION
SELECTION OF DISSOLUTION MEDIUM
TYPES OF DISSOLUTION MEDIA
COMPOSITION OF DISSOLUTION MEDIA
FACTOR AFFECTING DISSOLUTION MEDIA
REFERENCES
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3. Definition:-
Dissolution is the process by which a solid substance enters the
solvent phase to yield a solution i.e. mass transfer from solid
surface to liquid phase.
Importance:-
Dissolution testing is mainly used to confirm product quality and
batch-to-batch consistency.
In vitro dissolution testing is important in the case of poorly
water/aqueous soluble drug, where absorption and therapeutic
effects of drug depends on dissolution of drug in the medium.
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4. …Importance:-
Useful in Selection of excipient.
In R&D department, comparing In vitro dissolution data with In
vivo bioavailability, we would greatly facilitate product
development.
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5. The selection of an appropriate dissolution medium is a
fundamental stage of the dissolution test.
Selection of proper medium for dissolution testing depend upon
largely on physicochemical properties of drug.
The choice of the medium will depend on the purpose of the
dissolution test for batch to batch quality testing.
Selection of dissolution medium based in part solubility data and
dose range of drug product to ensure that sink condition are met.
So, we have to maintain sink condition in in-vitro. This is can be
achieved by-
1) Bathing the dissolving solid in fresh solvent from time to time
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6. 2) Increasing the volume of dissolution fluid.
3) Removing the dissolved drug by partitioning it from the aqueous
phase of the dissolution fluid into an organic phase placed either
above or below the fluid, for example, hexane or chloroform.
4) Adding a water miscible solvent such as alcohol to the
dissolution medium.
5) By adding selected adsorbent to remove the dissolved drug.
A sink condition occurs when the drug that can be dissolved in
the dissolution medium is 3 times greater than the amount of
drug to be dissolved.
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7. Primary requirement of selection of dissolution media is that it
should be able to reflect in vivo situation when it is used to
establish an IVIVC .
For class I and class III drugs use of simple aqueous media such
as SGF without enzyme or SIF is recommended.
For class II and class IV drug use of biorelevant media for
dissolution testing is recommended.
They are-
SGF plus surfactant.
Milk with 3.5 % fat to stimulate fed condition.
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9. Simulated Gastric Fluid (SGF) :-
The traditional medium to simulate gastric conditions in the
fasted state has been simulated gastric fluid (SGF) of the USP.
This medium contains hydrochloric acid and sodium chloride, as
well as pepsin and water, and has a pH of 1.2.
Although the medium addresses many of the qualities of gastric
juice, there are some aspects that could be optimized.
Simulated Intestinal Fluid (SIF) :-
A frequently used medium for the simulation of small intestinal
(SI) conditions in the fasted state is simulated intestinal fluid
(SIF), a medium that was first described as standard test solution
in the USP more than 50 years ago.
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10. ….Simulated Intestinal Fluid:-
The only parameter that has been changed is the pH of the
medium.
As it was assumed that the pH in the small intestine is very close
to blood plasma, the pH of SIF was initially set at 7.5.
However, subsequent examinations of the pH in the intestinal
tract revealed that a pH gradient exists within the small intestine,
that the pH becomes less acidic at more distal locations, and that
pH values close to 7.5.
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11. Water :-
Water is an attractive medium that because of its simplicity has
been widely used for quality control purposes.
However, the pH of water may vary with its source, and water
has no buffer capacity. Thus, for the latter purpose, a better
alternative, which would be more biorelevant in this context, is a
diluted HCl/NaCl solution or a diluted acetate buffer with a final
pH of around 5.
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12. Biorelevent Media:-
Biorelevant media are virtually the same as intestinal juices.
They contain key natural surfactants (bile salts, phospholipids)
present in intestinal juices. These are missing from ordinary
dissolution media.
They are virtually the same as the fluids inside the body, it can
provide a much more accurate picture of how drugs and their
formulations are likely to dissolve in vivo.
The aims are to highlight potential bioavailability issues and
attempt to achieve IVIVC.
Biorelevant media include Fasting state and Fed state simulated
Gastro Intestinal fluids.
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13. MEDIUM pH COMPOSITION AMOUNT
Simulated gastric
fluid(SGF )without
enzyme, USP
1.2 NaCl 2.0 g
Concentrated
HCl
7.0 ml
Deionised Water 1000 ml
Simulated gastric
fluid(SGF) with enzyme,
USP
1.2 NaCl
Concentrated
HCl
2.0 g
7.0 ml
Pepsin 3.2 g
Deionised Water 1000 ml
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14. MEDIUM pH COMPOSITION AMOUNT
Simulated intestinal fluid
(SIFsp ),USP 26
6.8 KH2PO4 68.05 g
NaOH 8.96 g
Deionised Water 1000 ml
Simulated intestinal fluid
(SIF ),USP 26
6.8 KH2PO4 68.05 g
NaOH 8.96 g
Deionised Water 1000 ml
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15. Dissolved gases
Composition and pH of dissolution media
Viscosity of dissolution media
Surfactants
Temperature of dissolution media
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16. Dissolved gases:-
Dissolved gas can alter the pH of media
Eg. Distilled water pH = 6
Deaerated water pH = 7.2
With change of temperature dissolved gas may released in form
of bubbles affecting dissolution.
To minimize the effect of dissolved gases, media should be
buffered.
According to USP, degassing of dissolution media before
dissolution study is very necessary.
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18. Helium sparging:-
Helium gas is used to continually bubble through media.
Helium gas degases liquid by absorbing the gases that are
dissolved in media, in to helium bubbles.
Disadvantages-
It is costly method as it requires constant supply of helium gas.
Media can become saturated with helium gas.
Vaccum degassing:-
Media need to held under vaccum, where it can possible to remove
more than 95% of dissolved gas.
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19. Heating and filtering:-
This method requires heating of dissolution media to 45oC,
followed by filtration through 0.45um filter membrane.
This method can remove 85% of dissolved oxygen.
Composition and pH of dissolution media:-
If dissolution media contains various ions and salts, it has
significant effect on dissolution of drugs.
Eg-Dissolution rate of benzoic acid from tablet decreases,
when various concentrations of sodium chloride, sodium sulfate
& dextrose are present in dissolution media.
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20. This effect occurs due to change in PH associated with addition
of salt.
Viscosity of dissolution media:-
Dissolution rate decreases with increase in viscosity of
dissolution medium in case of diffusion controlled dissolution
process.
Viscosity have very little effect on interfacial controlled
dissolution process.
Surfactants:-
Surfactants improve penetrability of dissolution media in to
matrix.
by lowering contact angle, thereby enhancing dissolution process
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21. Temperature of dissolution media:-
It is usually kept at 37+/-0.5oC in usual dissolution testing for all
type of dosage form.
Exception comes in case of transdermal drug delivery system
where temperature of dissolution media is kept 32oC .
Slightly increased temperatures such as 38±0.5°C have been
recommended for dosages forms such as suppositories.
Any change in temperature of dissolution medium may bring
about altered dissolution of dosage form.
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22. Indian pharmacopoeia, (2014) Published by Indian pharmacopoeia
commission indian pharmacopoeia laboratory government of india
ministry of health and family welfare Ghaziabad, volume-1, page no-
760.
Banakar, Umesh V. (1991) Pharmaceutical Dissolution Testing.
volume –1, Published by CRC Press, page no-176
Brahmankar, D. M And Jaiswal, Sunil B. (2009) A textbook of
Biopharmaceutics and Pharmacokinetics. 2nd Edition. Delhi, Vallabh
Prakashan, Page no-326.
Remington,(1995) The Science And Practice Of Pharmacy. volume-
1, 19th Edition. Easton Pennsylvania, Mack publishing Company,
page no-602.
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23. Mr. Ripal Mistry (1971) Selection Of Dissolution Media,
Available From www.Pharmatutor.Org (Accessed On 1 Oct 2014).
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