veena

Dissolution Test EquipmentUnder the guidance of

Mr . MA . Sirajuddeen M Pharm , DCT.( PhD )

Seminar Presented ByVeena Reddy . Singam

Roll no:05 , first year ,M Pharmacy ,Department of pharmaceutics.Omega College of pharmacy .

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Dissolution is a process in which a solid substance solubilizes in a given solvent i.e. mass transfer from the solid surface to the liquid phase.

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.

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DefinitionDefinition

Immediate release dosage forms• powders, granules / beads, tablets, capsules

Controlled release dosage forms• powders, granules / beads, tablets, capsules

Transdermal systems Implants

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Dosage forms to be tested

United States Pharmacopeia• UXX (30)SP X

European Pharmacopoeia• Ph. Eur. 5th Edition, Supplement 5.3

British Pharmacopoeia• BP 2007

Japanese Pharmacopoeia• JP XIV (14)

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Official Dissolution Monographs

USP 30 classification1.Rotating Basket (Ph.Eur./BP/JP)

2.Paddle (Ph.Eur./BP/JP)

3.Reciprocating Cylinder (Ph.Eur.)

4.Flow Through Cell (Ph.Eur./BP/JP)

5.Paddle Over Disk (Ph.Eur.)

6.Rotating Cylinder (Ph.Eur.)

7.Reciprocating Holder

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Official dissolution apparatus

Depends on intention1. Quality control

Examining batch homogeneity Examining batch to batch conformity Examining stability

2. Research & Development Examining drug release behavior of preformulations In vitro simulation of the gastrointestinal

passage

3. IVIVC 6

Which type of dissolution apparatus?

Design Consists of an approximately 1 inch (25.4mm)

× 1 3/8 inch (34.925mm) stainless steel, 40-mesh wire basket rotated at a constant speed between 25 and 150rpm.

The distance between the inside bottom of the vessel and the bottom of the basket is maintained at 25 ± 2 mm during the test.

A speed-regulating device is used that allows the shaft rotation speed to be selected and maintained at a specified rate, within ± 4 per cent.

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Apparatus 1 - Basket

Useful for• Capsules• Beads• Delayed release / enteric

coated dosage forms• Floating dosage forms• Surfactants in media

Standard volume• 900/1000 ml• 1, 2, 4 liter vessels

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Advantages• Breadth of experience

(more than 200 monographs)

• Full pH change during the test

• Can be easily automated which is important for routine investigations

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Disadvantages• Disintegration-dissolution

interaction

• Hydrodynamic dead zone under the basket

• Degassing is particularly important

• Limited volume sink conditions for poorly soluble drugs ?

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Design The specifications for Apparatus 2 are

identical with those for Apparatus 1 except that the paddle is substituted for the rotating basket.

The contours of the paddle blade must not include any sharp edges at the tips for instance that could produce turbulent instead of laminar flow patterns.

The USP suggests that paddles ‘may’ be coated with polyfluorocarbon and most commercial paddles are accordingly coated.

Rotation speed for solid dosage forms is 50 RPM, while for Liquid dosage forms (SUSPENSION) its 25 RPM.12

Apparatus 2 - paddle

Useful for• Tablets• Capsules• Beads• Delayed release / enteric

coated dosage forms

Standard volume• 900/1000 ml

Method of first choice !!!13


Advantages• Easy to use

• Robust

• Can be easily adapted to apparatus 5

• Long experience

• PH change possible

• Can be easily automated which is important for routine investigations

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Disadvantages• PH or media change is often difficult

• Limited volume sink conditions for poorly soluble drugs ?

• Hydrodynamics are complex, they vary with site of the dosage form in the vessel (sticking,floating) and therefore may significantly affect drug dissolution

• Coning

• Sinkers for floating dosage forms15


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Sinker types

JP/ USP / Ph. Eur. 5.3 Sinker

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Conning

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Design A set of cylindrical, flat-bottomed glass vessels; A set of glass reciprocating cylinders. Inert fittings (stainless steel type 316 or other

suitable material). Screens that are made of suitable nonsorbing

and nonreactive material, and that are designed to fit the tops and bottoms of the reciprocating cylinders;

A motor and drive assembly to reciprocate the cylinders vertically inside the vessels.

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Apparatus 3 – Reciprocting cylinder

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Useful for• Tablets• Beads• Controlled release formulations

Standard volume• 200-250 ml per station

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Advantages• Easy to change the pH• PH-profiles• Hydrodynamics can be

directly influenced by varying the dip rate

Disadvantages• Small volume (max. 250 ml)• Little experience• Limited data

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Design A pump for the dissolution medium. A flow-through cell. A water-bath to maintain the dissolution

medium at 37 ± 0.5°C. The pump forces the dissolution medium

upwards through the flow-through cell. The flow-through cell of transparent and inert

material is mounted vertically, with a filter system that prevents escape of undissolved particles from the top of the cell; standard cell diameters are 12 mm and 22.6 mm.

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Apparatus 4 –Flow-through cell

Useful for• Low solubility drugs• Microparticulates• Implants• Suppositories• Controlled release formulations

Variations• Open system• Closed system 24


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Cell types

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Apparatus 4 –Flow-through cell Advantages

• Easy to change media pH• PH-profile possible• Sink conditions• Different modes

a) Open systemb) Closed system

Disadvantages• Deaeration necessary

• High volumes of media

• Labor intensive

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Design• With paddle over disc, the transdermal patch is

placed between a glass disc and an inert PTFE (POLY TEFLON) mesh.

• This is placed at the bottom of the vessel, with the mesh facing upwards, under a rotating paddle.

• Unlike dissolution testing, transdermal testing is carried out at 32°C to reflect the lower temperature of the skin.

• USP 5 apparatus is made-up of borosilicate glass with a PTFE 17 mesh, held together by PTFE clips. Patches up to 90 mm in diameter can be tested.

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Apparatus 5 –Paddle over disk

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Useful for• Transdermal patches

Standard volume• 900 ml

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Advantages• Standard equipment

(paddle) can be used, only add a stainless steel disk assembly

Disadvantages• Disk assembly restricts

patch size

The cylinder consists of two parts that fit together: the main shaft/cylinder assembly plus an extension. The extension is used when the transdermal patch requires a larger area

Same as apparatus 1,except to replace the basket and shaft with a S.S. cylinder stirring element.

Temperature - 32 ± 0.5° The dosage unit is placed on the cylinder. Distance between the inside bottom of the vessel and

cylinder is maintained at 25 ± 2 mm. Transdermal or patch testing is carried out .

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Apparatus 6–Rotating cylinder

The assembly consists of a set of calibrated solution containers, a motor and drive assembly to reciprocate the system vertically.

Various type of sample holder are used The vessels are partially immersed in a suitable water-

bath of any convenient size that permits holding the temperature at 37 ± 0.5 °C during the test.

Cuprophan (Cellophane paper) is used for holding of semisolid dosage forms.

Useful for testing of extended release dosage forms, Osmotic pumps, Tablets, Ointments, Gels etc.

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USP Apparatus 7-Reciprocating holder

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Apparatus 6 – Rotating cylinder

USP apparatus 7 – Reciprocating holder

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Type of Dosage Form Apparatus

Conventional solid oral dosage form

Basket, paddle, reciprocating cylinder or flow through cell

Oral suspension Paddle

Orally disintegrating tablet Paddle

Chewable tablet Basket, paddle, or reciprocating cylinder with glass beads

Transdermal patch

Paddle over disk

Suppositories Paddle, modified basket, or dual chamber flow through cell

conclusion

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SummaryImmediate release dosage forms: apparatus 1 or 2 (preferably 2)

Controlled release dosage forms: apparatus 1 or 2 using different media for QC apparatus 3 or 4 for R&D purposes

Beside the selection of an adequate dissolution apparatus, adequate test conditions are crucial for all purposes !

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Suggested readingFIP Guidelines for dissolution testing of solid oral products.Dissolution Technologies 4:5-14 (1997).SM Diebold, JB Dressman . Dissolved oxygen as a measure for de- and re-aeration of aqueous media for dissolution testing. Dissolution Technologies 5: 13-16 (1998).S Qureshi . Calibration – the USP dissolution apparatus suitability test.Drug Inf. J. 30, 1055-1061 (1996).N Kaniwaet al. Collaborative study on the development of a standard for evaluation of vibration levels for dissolution apparatus . Int. J. Pharm. 175: 119-129 (1998).VA Gray, CK, Brown, JB Dressman, LJ Leeson. A new general information chapter on dissolution . Pharmacopoeial Forum 27 (6) [Nov.-Dec. 2001]W Brown. General information <1092> The dissolution procedure: development and validation Pharmacopoeial Forum 30 (1) [Jan.-Feb. 2004]

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