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Apparatus for Dissolution Testing

INTRODUCTION

  • The effectiveness of dosage forms relies on the drug dissolving in the fluids of the gastrointestinal tract prior to absorption into the systemic circulation. The rate of dissolution of the tablet or capsule is therefore crucial.
  • One of the problems facing the pharmaceutical industry is to optimize the amount of drug available to the body, i.e. its ‘bioavailability’. Inadequacies in bioavailability can mean that the treatment is ineffective and at worst potentially dangerous (toxic overdose).
  • Drug release in the human body can be measured ‘in-vivo’ by measuring the plasma or urine concentrations in the subject concerned. However, there are certain obvious impracticalities involved in employing such techniques on a routine basis. These difficulties have led to the introduction of official ‘in-vitro’ tests which are now rigorously and comprehensively defined in the respective Pharmacopoeia.
  • Dissolution is a standardized method for measuring the rate of drug release from a dosage form.
  • Although initially developed for oral dosage forms, the role of the dissolution test has now been extended to ‘drug release’ studies on various other forms such as topical and transdermal systems and suppositories.

APPARTUS FOR DISSOLUTION TESTING

As per IP

Two types of apparatus are specified

  • APPARATUS 1 (BASKET APPARATUS)
  • APPARATUS 2 (PADDLE APPARATUS)

As per USP

Seven types of apparatus are specified…

  • APPARATUS 1 (BASKET APPARATUS)
  • APPARATUS 2 (PADDLE APPARATUS)
  • APPARATUS 3 (RECIPROCATING CYLINDER)
  • APPARATUS 4 (FLOW THROUGH CELL)
  • APPARATUS 5 (PADDLE OVER DISK)
  • APPARATUS 6 (ROTATING CYLINDER)
  • APPARATUS 7 (RECIPROCATING HOLDER)

APPARATUS 1

(BASKET APPARATUS)

  • Adopted in 1970 the rotating basket method of dissolution testing was the first official method. Essentially it consisted 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. This method is now called Apparatus 1.
  • The apparatus consists a metallic drive shaft connected to the cylindrical basket. The basket is positioned inside a vessel made of glass or other inert, transparent material. The temperature inside the vessel is kept at a constant temperature by being placed inside a water bath or heating jacket. The solution in the vessel is stirred smoothly by the rotating stirring element.
  • 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.
  • Shaft and basket components of the stirring element are fabricated of stainless steel, type 316 or equivalent, to the specifications shown in Figure.
  • A basket having a gold coating of about 2.5 µm (0.0001 inch) thick may be used. The dosage unit is placed in a dry basket at the beginning of each test.
  • The distance between the inside bottom of the vessel and the bottom of the basket is maintained at 25 ± 2 mm during the test.
  • Other types of basket exist for specific applications. For example, suppository baskets are normally manufactured from plastic and have vertical slits to facilitate the dissolution.
  • Japanese baskets are sometimes confused with dissolution baskets although they are actually sinkers. Products manufactured under the JP may require the use of this basket.
  • This apparatus is used mainly for testing of uncoated tablets, Enteric coated tablets, Sublingual tablets, hard gelatin capsules and Soft gelatin capsules.

MODIFICATIONS

(i) WATERLESS BATH DISSOLUTION APPARATUS

Here vessels are heated with a water jacket, not submerged into a water-bath.

(ii) PEAK VESSELS

Its having a cone shaped glass vessel.

Mainly useful for the products having dense excipients, which are having tendency to cone rather than to disperse freely inside the vessel.

e.g. Guar Gum, Ethyl Cellulose etc.

(iii) CLIP & CLIPLESS BASKETS

It helps to retain tablet in proper position.

Spring Clips are official in USP while ‘O’ Rings are non-official.

MEDIA DEGASSING

There are various methods of degassing media —

Helium sparging,

Warming, and subsequent filtering and

Vacuum degassing are the most popular.

The method suggested in the USP is to heat the media to 45°C then filter it through a 0.45µm filter under vacuum and stirred for about 5 minutes before being placed directly into the dissolution vessel.

This method of degassing has been shown to reduce the level of dissolved gases by about 85% which is enough to ensure that the air will not affect the dissolution results.

METHODS FOR DEAERATION

  • Helium sparging can be effective but is costly to use for large volumes, as it requires a constant supply of helium gas to continually bubble through the media.
  • It degasses the liquid by absorbing the gases that are dissolved in the media into the helium bubbles and carrying them out of solution.
  • One of the major problems with this method is that the media can become saturated with helium which causes similar problems to being saturated with air and it is difficult to measure the amount of helium in the liquid.
  • Heating and filtering the media is fairly reliable and is the method described in USP 23 (it actually specifies heating to 45 °C, followed by filtration through a 0.45µm filter membrane).
  • This will remove about 85% of the dissolved oxygen, although the media then has to be cooled before the dissolution test which gives it time to reaerate.
  • Vacuum degassing can remove more than 95% of the dissolved gas and if the media is held under vacuum then it will not be able to reaerate before it is placed in the dissolution vessel.
  • Other common laboratory methods of degassing such as sonication or membrane degassing are not practical for degassing the large volumes required for dissolution testing and are more suited for HPLC.

 

METHOD % REDUCTION (APPROXIMATE)
USP 84.9 ±   11%
Filtering only at room temperature 65 ± 3%
Heating   to 45°C 10 ± 14%
Boiling 49 ± 3%
Vacuum   degassing 50-90%

 

APPARATUS 2 (PADDLE)

  • Apparatus 2, commonly known as the paddle method, was originally developed by Poole (1969) and was refined by scientists at the FDA for Drug Analysis in St Louis. The specifications for Apparatus 2 are identical with those for Apparatus 1 except that the paddle is substituted for the rotating basket.
  • The USP specifies that the paddle must rotate smoothly without significant wobble. The arc of the paddle blade creates considerable flow and wobble has the effect of increasing the angular velocity at the paddle tips in a manner that couples with the fluid much more significantly than would a comparable wobble in the 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 constrains wobble and vertical alignment with the axis of the vessel to within ±2.0mm.
  • The USP suggests that paddles ‘may’ be coated with polyfluorocarbon and most commercial paddles are accordingly coated.
  • Such coating serves two purposes: it prevents corrosion and the introduction of unwanted ions into the media and it seals the joint where the blade is attached to the shaft, thus preventing the accumulation of traces of contaminants.
  • Because of the precise geometry required for the repeatability of the paddle method, the stirring paddle has been specified as a stainless steel device rather than a glass one with a detachable blade, largely because glass cannot be manufactured to such close cost specifications without incurring excessive cost.
  • Rotation speed for solid dosage forms is 50 RPM, while for Liquid dosage forms (SUSPENSION) its 25RPM.
  • It cannot be used for testing of POWDER DOSAGE FORMS.
  • This apparatus is used mainly for testing of uncoated tablets, Enteric coated tablets, Sublingual tablets, hard gelatin capsules and Soft gelatin capsules, Gels, Ointments.

 

APPARATUS 3 (RECIPROCATING CYLINDER)

The assembly consists of

  • A set of cylindrical, flat-bottomed glass vessels;
  • A set of glass reciprocating cylinders.
  • Inert fittings (stainless steel type 316 or other suitable material) and
  • 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.
  • 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.
  • A device is used that allows the reciprocation rate to be selected and maintained at the specified dip rate, within ± 5 per cent.
  • This apparatus resembles the Disintegration apparatus.
  • Upward and downward strokes of cylinder are observed.
  • It’s quite useful for beaded products like pellets, granules etc.
  • Also useful for controlled and immediate release products.

APPARATUS 4 (FLOW THROUGH CELL)

The assembly consists of

  • 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 pump has a delivery range between 240 ml/h and 960 ml/h, with standard flow rates of 4 ml/min, 8 ml/min, and 16 ml/min. It must deliver a constant flow (± 5 % of the nominal flow rate). Non-pulsated flow may also be used.
  • 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; the bottom cone is usually filled with small glass beads of about 1 mm diameter, with 1 bead of about 5 mm positioned at the apex to protect the fluid entry tube; a tablet holder is available for positioning of special dosage forms. The cell is immersed in a water-bath, and the temperature is maintained at 37 ± 0.5 °C
  • Its mainly used for testing of Sugar coated tablets, Suppositories, Semisolid dosage forms, Powder, Granules, Implants.

 

APPARATUS 5 (PADDLE OVER DISK)

  • Transdermal or patch testing is carried out using USP method 5 (paddle over disc).
  • 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. Other variables such as the height setting and sampling requirements are the same as dissolution testing.
  • USP 5 apparatus is made-up of borosilicate glass with a PTFE 17 mesh, held together by PTFE clips. Patches up to 90mm in diameter can be tested.

APPARATUS 6 (ROTATING CYLINDER)

  • Transdermal or patch testing is carried out using USP method 5 (paddle over disc) or USP method 6, the rotating cylinder.
  • The rotating cylinder is very similar to USP method 1 (the rotating basket).
  • With USP method 6 however, the basket assembly is replaced by a solid stainless steel 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.
  • The distance between the inside bottom of the vessel and the cylinder is maintained at 25 ± 2 mm during the test.
  • The temperature is maintained at 32 ± 0.5 °C. The vessel is covered during the test to minimize evaporation.

 

APPARATUS 7 (RECIPROCATING HOLDER)

 

  • 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.
  • A device is used that allows the reciprocation rate to be selected and maintained at the specified dip rate, within ± 5 per cent.
  • Useful for testing of extended release dosage forms, Osmotic pumps, Tablets, Ointments, Gels etc.
  • Cuprophan (Cellophane paper) is used for holding of semisolid dosage forms.

 

FIBRE OPTIC DISSOLUTION TECHNIQUE

  • In the first instance the introduction of tablets or other dosage forms is as with a conventional dissolution instrument.
  • The instrument is operated by WINDISS 32 Dissolution Software control.
  • The sampling sequences have been replaced by direct measurement technology within the dissolution vessel itself, with each measurement cycle accomplished in seconds .
  • The in situ measurement is carried out using fibre optic probes which are located in the shafts of the dissolution tools, i.e., a paddle or a basket (Apparatus 2 or 1).
  • The fibre optic probe can be removed from the shaft so that various path length inserts can be employed for different active concentrations ranges.
  • The fibre optic probe can then be simply reinserted into the tool shaft and the next analysis started.

ADVANTAGES:-

  • It’s an automated process.
  • Less time consuming method.
  • Optic fibre probes are used, so sampling is not required.
DISSOLUTION APPARATUS USES
Basket Apparatus Capsule
Paddle Apparatus Tablet
Reciprocating Cylinder SR, Beads
Flow through cell Low solubility drug
Paddle over Disk Transdermal Patches, Ointments, Gels, Emulsion
Rotating Cylinder Transdermal Patches, Ointments, Gels, Emulsion
Reciprocating Holder Transdermal Patches, Ointments, Gels, Emulsion

 

METHODS FOR DEAERATION

  • Helium sparging can be effective but is costly to use for large volumes, as it requires a constant supply of helium gas to continually bubble through the media.
  • It degasses the liquid by absorbing the gases that are dissolved in the media into the helium bubbles and carrying them out of solution.
  • One of the major problems with this method is that the media can become saturated with helium which causes similar problems to being saturated with air and it is difficult to measure the amount of helium in the liquid.
  • Heating and filtering the media is fairly reliable and is the method described in USP 23 (it actually specifies heating to 45 °C, followed by filtration through a 0.45µm filter membrane).
  • This will remove about 85% of the dissolved oxygen, although the media then has to be cooled before the dissolution test which gives it time to reaerate.
  • Vacuum degassing can remove more than 95% of the dissolved gas and if the media is held under vacuum then it will not be able to reaerate before it is placed in the dissolution vessel.
  • Other common laboratory methods of degassing such as sonication or membrane degassing are not practical for degassing the large volumes required for dissolution testing and are more suited for HPLC.

1 responses on "Apparatus for Dissolution Testing"

  1. Thank you for your blog! Keep up the good work! Much Thanks!

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