Dissolution Test Equipment

Under the guidance of Mr . MA . Sirajuddeen M Pharm , DCT.( PhD ) Seminar Presented By Veena Reddy . Singam Roll no:05 , first year ,M Pharmacy , Department of pharmaceutics. Omega College of pharmacy . 1

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.

Definition Definition

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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Dosage forms to be tested

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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Official Dissolution Monographs

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 apparatus

USP 30 classification
1. 2. 3. 4. 5. 6. 7. Rotating Basket (Ph.Eur./BP/JP) Paddle (Ph.Eur./BP/JP) Reciprocating Cylinder (Ph.Eur.) Flow Through Cell (Ph.Eur./BP/JP) Paddle Over Disk (Ph.Eur.) Rotating Cylinder (Ph.Eur.) Reciprocating Holder
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Which type of dissolution apparatus?

Depends on intention
1. Quality control

Examining batch homogeneity Examining batch to batch conformity Examining stability

Examining drug release behavior of preformulations In vitro simulation of the gastrointestinal passage

2. Research & Development

3. IVIVC
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Apparatus 1 - Basket
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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Apparatus 1 - Basket
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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Apparatus 1 - Basket
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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Apparatus 1 - Basket

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Design

Apparatus 2 - paddle

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.
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Apparatus 2 - paddle
Useful for
Tablets Capsules Beads Delayed release / enteric coated dosage forms

Standard volume
900/1000 ml

Method of first choice !!!

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Apparatus 2 - paddle
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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Apparatus 2 - paddle
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 forms 15

Sinker types

JP/ USP / Ph. Eur. 5.3 Sinker

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Conning

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Apparatus 2 - paddle

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Apparatus 3 Reciprocting cylinder

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

Useful for

Tablets Beads Controlled release formulations

Standard volume

200-250 ml per station

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Apparatus 3 Reciprocting cylinder

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 21

Apparatus 3 Reciprocting cylinder

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Apparatus 4 Flow-through cell

Design
A pump for the dissolution medium. A flow-through cell. A water-bath to maintain the dissolution medium at 37 0.5C. 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 23 mm and 22.6 mm. 12

Apparatus 4 Flow-through cell

Useful for
Low solubility drugs Microparticulates Implants Suppositories Controlled release formulations

Variations
Open system Closed system
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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 system b) Closed system

Deaeration necessary High volumes of media Labor intensive

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Disadvantages

Apparatus 4 Flow-through cell

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Apparatus 5 Paddle over disk

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 32C 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 28 to 90 mm in diameter can be tested.

Apparatus 5 Paddle over disk

Useful for
Transdermal patches

Standard volume
900 ml

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Apparatus 5 Paddle over disk

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

Disadvantages
Disk assembly restricts patch size
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Apparatus 6Rotating cylinder

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 . 31

 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 waterbath 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

Apparatus 6 Rotating cylinder USP apparatus 7 Reciprocating holder

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conclusion
Type of Dosage Form Conventional solid oral dosage form Oral suspension Orally disintegrating tablet Chewable tablet Transdermal patch Suppositories Apparatus Basket, paddle, reciprocating cylinder or flow through cell Paddle Paddle Basket, paddle, or reciprocating cylinder with glass beads Paddle over disk Paddle, modified basket, or dual chamber flow through cell
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Summary
Immediate 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 reading
FIP 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 reaeration 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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QUESTIONS...........

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