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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INRODUCTION

SELECTION OF DISSOLUTION MEDIUM

TYPES OF DISSOLUTION MEDIA

COMPOSITION OF DISSOLUTION MEDIA

FACTOR AFFECTING DISSOLUTION MEDIA

REFERENCES

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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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…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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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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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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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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Simulated Gastric Fluid

Simulated Intestinal Fluid

Water

Biorelevent Media

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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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….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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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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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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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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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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Dissolved gases

Composition and pH of dissolution media

Viscosity of dissolution media

Surfactants

Temperature of dissolution media

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Dissolved gases:-

Dissolved gas can alter the pH of mediaEg. Distilled water pH = 6

Deaerated water pH = 7.2

With change of temperature dissolved gas may released in formof bubbles affecting dissolution.

To minimize the effect of dissolved gases, media should bebuffered.

According to USP, degassing of dissolution media beforedissolution study is very necessary.

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Methods of degassing:-

Helium sparging

Vaccum degassing

Heating and filtering

Boiling

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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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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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This effect occurs due to change in PH associated with additionof salt.

Viscosity of dissolution media:-

Dissolution rate decreases with increase in viscosity ofdissolution medium in case of diffusion controlled dissolutionprocess.

Viscosity have very little effect on interfacial controlleddissolution process.

Surfactants:-

Surfactants improve penetrability of dissolution media in to

matrix.

by lowering contact angle, thereby enhancing dissolution process

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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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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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Mr. Ripal Mistry (1971) Selection Of Dissolution Media,

Available From www.Pharmatutor.Org (Accessed On 1 Oct 2014).

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